Publications by authors named "Christopher J Scarlett"

80 Publications

Sour Taste SNP -rs236514 and Differences in Nutrient Intakes and Metabolic Health Markers in the Elderly.

Front Nutr 2021 17;8:701588. Epub 2021 Aug 17.

School of Environmental and Life Sciences, The University of Newcastle, Ourimbah, NSW, Australia.

Single nucleotide polymorphisms (SNPs) in taste receptors influence dietary choices that contribute to health and quality of life. Individual differences in sour taste perception and preference have been linked to heritable genetics, yet the impact of sour taste receptor SNPs on sour taste is under-researched, and studies on sour taste SNP associations to diet and health are lacking. Therefore, this study explored the relationships between the sour taste SNP -rs236514 and estimated macronutrient, vitamin and mineral intakes, and markers of metabolic health. Associations were explored in 523 participants aged 65 years and older with data analysed using standard least squares and nominal logistic regression modelling with student's -tests and Tukey's HSD. Associations were found between the presence of the -rs236514 variant allele (A) and lower intakes of energy, total fat, monounsaturated fat and saturated fat. The lower fat intakes were significant in female carriers of the variant allele (A), along with lower water intake. Lower retinol, riboflavin, folate, calcium and sodium intakes were found in the -A allele carriers. In females, the variant allele was associated with lower sodium intake before and after Bonferroni adjustment. Higher body mass index, waist and waist-to-hip ratio measures were found in males carrying the variant allele. Lower levels of liver function biomarkers were associated with the presence of the -A allele. Overall and in males, the variant's association to lower gamma-glutamyl transferase (GGT) levels remained significant after Bonferroni adjustments. These novel findings suggest the sour taste SNP, -rs236514, may be modifying macronutrient, vitamin and mineral intakes, and markers of metabolic health. Research on the extra-oral functions of this SNP may improve health outcomes for those with overweight, obesity and liver disease.
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http://dx.doi.org/10.3389/fnut.2021.701588DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415820PMC
August 2021

Biophysical evidence to support and extend the vitamin D-folate hypothesis as a paradigm for the evolution of human skin pigmentation.

Am J Hum Biol 2021 Aug 21:e23667. Epub 2021 Aug 21.

School of Environmental and Life Sciences, University of Newcastle, Ourimbah, New South Wales, Australia.

Objective: To test the "vitamin D-folate hypothesis for the evolution of human skin pigmentation."

Methods: Total ozone mapping spectrometer (TOMS) satellite data were used to examine surface UV-irradiance in a large (n = 649) Australian cross-sectional study population. Genetic analysis was used to score vitamin D- and folate-related gene polymorphisms (n = 22), along with two pigmentation gene variants (IRF4-rs12203592/HERC2-rs12913832). Red cell folate and vitamin D were measured by immunoassay and HPLC, respectively.

Results: Ultraviolet radiation (UVR) and pigmentation genes interact to modify blood vitamin levels; Light skin IRF4-TT genotype has greatest folate loss while light skin HERC2-GG genotype has greatest vitamin D synthesis (reflected in both TOMS and seasonal data). UV-wavelength exhibits a dose-response relationship in folate loss within light skin IRF4-TT genotype (305 > 310 > 324 > 380 nm). Significant vitamin D photosynthesis only occurs within light skin HERC2-GG genotype, and is maximal at 305 nm. Three dietary antioxidants (vitamins C, E, and β-carotene) interact with UVR and pigmentation genes preventing oxidative loss of labile reduced folate vitamers, with greatest benefit in light skin IRF4-TT subjects. The putative photosensitiser, riboflavin, did not sensitize red cell folate to UVR and actually afforded protection. Four genes (5xSNPs) influenced blood vitamin levels when stratified by pigmentation genotype; MTHFR-rs1801133/rs1801131, TS-rs34489327, CYP24A-rs17216707, and VDR-ApaI-rs7975232. Lightest IRF4-TT/darkest HERC2-AA genotype combination (greatest folate loss/lowest vitamin D synthesis) has 0% occurrence. The opposing, commonest (39%) compound genotype (darkest IRF4-CC/lightest HERC2-GG) permits least folate loss and greatest synthesis of vitamin D .

Conclusion: New biophysical evidence supports the vitamin D-folate hypothesis for evolution of skin pigmentation.
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http://dx.doi.org/10.1002/ajhb.23667DOI Listing
August 2021

Cytotoxic 1,2,3-Triazoles as Potential Leads Targeting the S100A2-p53 Complex: Synthesis and Cytotoxicity.

ChemMedChem 2021 Sep 12;16(18):2864-2881. Epub 2021 Jul 12.

Chemistry, School of Environmental & Life Sciences The University of Newcastle, University Drive, Callaghan, NSW 2308, Australia.

In silico screening predicted 1 (N-(4-((4-(3-(4-(3-methoxyphenyl)-1H-1,2,3-triazol-1-yl)propyl)piperazin-1-yl) sulfonyl)-phenyl)acetamide) as an inhibitor of the S100A2-p53 protein-protein interaction. S100A2 is a validated pancreatic cancer drug target. In the MiaPaCa-2 pancreatic cell line, 1 was a ∼50 μM growth inhibitor. Synthesis of five focused compound libraries and cytotoxicity screening revealed increased activity from the presence of electron withdrawing moieties on the sulfonamide aromatic ring, with the 3,5-bis-CF Library 3 analogues the most active, with GI values of 0.91 (3-ClPh; 13 i; BxPC-3, Pancreas) to 9.0 μM (4-CH ; 13 d; PANC-1, Pancreas). Activity was retained against an expanded pancreatic cancer cell line panel (MiaPaCa-2, BxPC-3, AsPC-1, Capan-2, PANC-1 and HPAC) and the normal cell line MCF10A (breast). Bulky 4-disposed substituents on the terminal phenyl ring enhanced broad spectrum activity with growth inhibition values spanning 1.1 to 3.1 μM (4-C(CH ) ; 13 e; BxPC-3 and AsPC-1 (pancreas), respectively). Central alkyl spacer contraction from propyl to ethyl proved detrimental to activity with Library 4 and 5.5- to 10-fold less cytotoxic than the propyl linked Library 2 and Library 3. The data herein was consistent with the predicted binding poses of the compounds evaluated. The highest levels of cytotoxicity were observed with those analogues best capable of adopting a near identical pose to the p53-peptide in the S100A2-p53 binding groove.
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http://dx.doi.org/10.1002/cmdc.202000950DOI Listing
September 2021

Targeting the S100A2-p53 Interaction with a Series of 3,5-Bis(trifluoromethyl)benzene Sulfonamides: Synthesis and Cytotoxicity.

ChemMedChem 2021 Sep 13;16(18):2851-2863. Epub 2021 Jul 13.

Chemistry, School of Environmental & Life Sciences, The University of Newcastle, University Drive, Callaghan, NSW, 2308, Australia.

In silico approaches identified 1, N-(6-((4-bromo- benzyl)amino)hexyl)-3,5-bis(trifluoromethyl)benzene sulfonamide, as a potential inhibitor of the S100A2-p53 protein-protein interaction, a validated pancreatic cancer drug target. Subsequent cytotoxicity screening revealed it to be a 2.97 μM cell growth inhibitor of the MiaPaCa-2 pancreatic cell line. This is in keeping with our hypothesis that inhibiting this interaction would have an anti-pancreatic cancer effect with S100A2, the validated PC drug target. A combination of focused library synthesis (three libraries, 24 compounds total) and cytotoxicity screening identified a propyl alkyl diamine spacer as optimal; the nature of the terminal phenyl substituent had limited impact on observed cytotoxicity, whereas N-methylation was detrimental to activity. In total 15 human cancer cell lines were examined, with most analogues showing broad-spectrum activity. Near uniform activity was observed against a panel of six pancreatic cancer cell lines: MiaPaCa-2, BxPC-3, AsPC-1, Capan-2, HPAC and PANC-1. In all cases there was good to excellent correlation between the predicted docking pose in the S100A2-p53 binding groove and the observed cytotoxicity, especially in the pancreatic cancer cell line with high endogenous S100A2 expression. This supports S100A2 as a pancreatic cancer drug target.
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http://dx.doi.org/10.1002/cmdc.202000949DOI Listing
September 2021

Assessment and comparison of phytochemicals and antioxidant properties from various parts of the Australian maroon bush ().

Heliyon 2021 Apr 18;7(4):e06810. Epub 2021 Apr 18.

School of Environmental and Life Sciences, University of Newcastle, Brush Rd., Ourimbah, NSW 2258, Australia.

is endemic to Australia and traditionally used as a medicinal plant. While its bioactive compounds have been studied, their concentrations in different parts of the plant have not been reported. This study compared total phenolic content (TPC), flavonoids, saponins and antioxidant properties, as well as major individual phytochemical compounds in the whole root, root bark, root wood, whole stem, stem bark, stem wood, and leaf of . The results showed the leaf had significantly highest concentrations of TPC followed by the root bark and stem bark (47.34, 12.24 and 10.20 mg GAE/g, respectively). Flavonoids concentrations were also significantly higher in the leaf compared to the root bark and stem bark (20.95, 6.22 and 4.19 mg CE/g, respectively). For saponins, the root bark contained significantly highest concentrations (112.58 mg EE/g). Luteolin 7-glucoside was isolated and identified in the leaf of Eight major compounds were identified with the leaf displaying the highest diversity of major compounds, and in higher concentrations, compared to the other plant constituents. As the leaf and root bark contained the highest concentrations of phytochemicals, these plant parts are recommended as starting material for future studies, to further isolate and identify the major compounds from and investigate their biological properties for use in pharmaceutical and food applications.
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http://dx.doi.org/10.1016/j.heliyon.2021.e06810DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082193PMC
April 2021

Ethnopharmacology, Biological Activity and Phytochemistry of Scaevola spinescens.

Chem Biodivers 2021 May 15;18(5):e2001050. Epub 2021 Apr 15.

School of Environmental and Life Sciences, University of Newcastle, Brush Rd., Ourimbah, NSW 2258, Australia.

Scaevola spinescens is endemic to Australia and has traditionally been used by Aboriginal and Torres Strait Islander communities to treat a variety of conditions including colds, flu, fever, stomach pain, urinary disorders, sores, tinea, leprosy, and cancer. Extracts prepared from S. spinescens are non-toxic and have been linked with various medicinal properties including antiviral, antibacterial, anti-inflammatory, and anticancer activities. These studies support the ethnopharmacological use of S. spinescens by Indigenous peoples of Australia and highlight the need for further investigations on the plant for potential use in pharmaceutical and food applications. This review provides a comprehensive, up-to-date review of the literature on S. spinescens focusing on the traditional use, medicinal properties, phytochemicals, and factors that affect their composition during pre-treatment and extraction, as well as providing a framework for future studies of the plant.
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http://dx.doi.org/10.1002/cbdv.202001050DOI Listing
May 2021

Genetic Variation in the Bitter Receptors Responsible for Epicatechin Detection Are Associated with BMI in an Elderly Cohort.

Nutrients 2021 Feb 9;13(2). Epub 2021 Feb 9.

School of Environmental and Life Sciences, University of Newcastle, Ourimbah 2258, Australia.

Globally, more than one-third of adults are overweight. Overweight and obesity are complex and multifaceted conditions, associated with an increased risk of chronic illness and early mortality. While there are known risk factors, these alone do not fully explain the varying outcomes between individuals. Recently, taste receptors have been proposed to have a role in the risk for obesity. These receptors are expressed throughout the gastrointestinal tract. In this system, they may be involved in modulating dietary intake and metabolic processes. The taste 2 family of receptors (T2Rs) detects bitter compounds. Receptors T2R4 and T2R5 detect (-)-epicatechin (epicatechin), an antioxidant polyphenol, which may have protective effects against obesity. However, the potential role for taste receptors in this association has not been explored. This study assessed whether polymorphisms in (rs2233998 and rs2234001) and (rs2227264) were associated with body mass index (BMI). Genotyping (Taqman qPCR assays) was performed on DNA extracted from blood samples ( = 563) from an elderly cohort. Homozygosity for the minor allele of all polymorphisms was significantly associated with a lower BMI in males. The -rs2233998 CC genotype, the -rs2234001 CC genotype and the -rs2227264 TT genotype were associated with lower BMI (2.1, 2.1 and 2.2 units; = 0.002, 0.003 and 0.001, respectively). Epicatechin intake was not associated with BMI and genotype was not associated with epicatechin intake. This suggests that the association between genotype and elevated BMI risk occurs through altered extra-oral responses and not directly via altered epicatechin intake.
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http://dx.doi.org/10.3390/nu13020571DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914776PMC
February 2021

Small molecule inhibitors in pancreatic cancer.

RSC Med Chem 2020 Feb 24;11(2):164-183. Epub 2020 Jan 24.

Chemistry , School of Environmental & Life Sciences , The University of Newcastle , Newcastle , Callaghan , NSW 2308 , Australia . Email: ; ; Tel: +61 249216486.

Pancreatic cancer (PC), with a 5 year survival of <7%, is one of the most fatal of all human cancers. The highly aggressive and metastatic character of this disease poses a challenge that current therapies are failing, despite significant efforts, to meet. This review examines the current status of the 35 small molecule inhibitors targeting pancreatic cancer in clinical trials and the >50 currently under investigation. These compounds inhibit biological targets spanning protein kinases, STAT3, BET, HDACs and Bcl-2 family proteins. Unsurprisingly, protein kinase inhibitors are overrepresented. Some trials show promise; a phase I combination trial of vorinostat and capecitabine gave a median overall survival (MoS) of 13 months and a phase II study of pazopanib showed a MoS of 25 months. The current standard of care for metastatic pancreatic ductal adenocarcinoma, fluorouracil/folic acid (5-FU, Adrucil®), and gemcitabine (GEMZAR®) afforded a MoS of 23 and 23.6 months (EPAC-3 study), respectively. In patients who can tolerate the FOLFIRINOX regime, this is becoming the standard of treatment with a MoS of 11.1 months. Clinical study progress has been slow with limited improvement in patient survival relative to gemcitabine monotherapy. A major cause of low PC survival is the late stage of diagnosis, occurring in patients who consider typical early stage warning signs of aches and pains normal. The selection of patients with specific disease phenotypes, the use of improved efficient drug combinations, the identification of biomarkers to specific cancer subtypes and more effective designs of investigation have improved outcomes. To move beyond the current dire condition and paucity of PC treatment options, determination of the best regimes and new treatment options is a challenge that must be met. The reasons for poor PC prognosis have remained largely unchanged for 20 years. This is arguably a consequence of significant changes in the drug discovery landscape, and the increasing pressure on academia to deliver short term 'media' friendly short-term news 'bites'. PC research sits at a pivotal point. Perhaps the greatest challenge is enacting a culture change that recognises that major breakthroughs are a result of blue sky, truly innovative and curiosity driven research.
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http://dx.doi.org/10.1039/c9md00447eDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7433757PMC
February 2020

Precision Oncology in Surgery: Patient Selection for Operable Pancreatic Cancer.

Ann Surg 2020 08;272(2):366-376

Department of Surgery, Universitätsklinikum Erlangen, Erlangen, Germany.

Objective: We aimed to define preoperative clinical and molecular characteristics that would allow better patient selection for operative resection.

Background: Although we use molecular selection methods for systemic targeted therapies, these principles are not applied to surgical oncology. Improving patient selection is of vital importance for the operative treatment of pancreatic cancer (pancreatic ductal adenocarcinoma). Although surgery is the only chance of long-term survival, 80% still succumb to the disease and approximately 30% die within 1 year, often sooner than those that have unresected local disease.

Method: In 3 independent pancreatic ductal adenocarcinoma cohorts (total participants = 1184) the relationship between aberrant expression of prometastatic proteins S100A2 and S100A4 and survival was assessed. A preoperative nomogram based on clinical variables available before surgery and expression of these proteins was constructed and compared to traditional measures, and a postoperative nomogram.

Results: High expression of either S100A2 or S100A4 was independent poor prognostic factors in a training cohort of 518 participants. These results were validated in 2 independent patient cohorts (Glasgow, n = 198; Germany, n = 468). Aberrant biomarker expression stratified the cohorts into 3 distinct prognostic groups. A preoperative nomogram incorporating S100A2 and S100A4 expression predicted survival and nomograms derived using postoperative clinicopathological variables.

Conclusions: Of those patients with a poor preoperative nomogram score, approximately 50% of patients died within a year of resection. Nomograms have the potential to improve selection for surgery and neoadjuvant therapy, avoiding surgery in aggressive disease, and justifying more extensive resections in biologically favorable disease.
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http://dx.doi.org/10.1097/SLA.0000000000003143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7373491PMC
August 2020

Intense Sweeteners, Taste Receptors and the Gut Microbiome: A Metabolic Health Perspective.

Int J Environ Res Public Health 2020 06 8;17(11). Epub 2020 Jun 8.

School of Environmental and Life Sciences, University of Newcastle, Ourimbah 2258, Australia.

Intense sweeteners (IS) are often marketed as a healthier alternative to sugars, with the potential to aid in combating the worldwide rise of diabetes and obesity. However, their use has been counterintuitively associated with impaired glucose homeostasis, weight gain and altered gut microbiota. The nature of these associations, and the mechanisms responsible, are yet to be fully elucidated. Differences in their interaction with taste receptors may be a potential explanatory factor. Like sugars, IS stimulate sweet taste receptors, but due to their diverse structures, some are also able to stimulate bitter taste receptors. These receptors are expressed in the oral cavity and extra-orally, including throughout the gastrointestinal tract. They are involved in the modulation of appetite, glucose homeostasis and gut motility. Therefore, taste genotypes resulting in functional receptor changes and altered receptor expression levels may be associated with metabolic conditions. IS and taste receptors may both interact with the gastrointestinal microbiome, and their interactions may potentially explain the relationship between IS use, obesity and metabolic outcomes. While these elements are often studied in isolation, the potential interactions remain unexplored. Here, the current evidence of the relationship between IS use, obesity and metabolic outcomes is presented, and the potential roles for interactions with taste receptors and the gastrointestinal microbiota in modulating these relationships are explored.
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http://dx.doi.org/10.3390/ijerph17114094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7312722PMC
June 2020

Independent and Interactive Influences of Environmental UVR, Vitamin D Levels, and Folate Variant -rs2236225 on Homocysteine Levels.

Nutrients 2020 May 18;12(5). Epub 2020 May 18.

School of Environmental & Life Sciences, University of Newcastle, Ourimbah, NSW 2258, Australia.

Elevated homocysteine (Hcy) levels are a risk factor for vascular diseases. Recently, increases in ultraviolet radiation (UVR) have been linked to decreased Hcy levels. This relationship may be mediated by the status of UVR-responsive vitamins, vitamin D and folate, and/or genetic variants influencing their levels; however, this has yet to be examined. Therefore, the independent and interactive influences of environmental UVR, vitamin D and folate levels and related genetic variants on Hcy levels were examined in an elderly Australian cohort ( = 619). Red blood cell folate, 25-hydroxyvitamin D (25(OH)D), and plasma Hcy levels were determined, and genotyping for 21 folate and vitamin D-related variants was performed. Erythemal dose rate accumulated over six-weeks (6W-EDR) and four-months (4M-EDR) prior to clinics were calculated as a measure of environmental UVR. Multivariate analyses found interactions between 6W-EDR and 25(OH)D levels (p = 0.002), and 4M-EDR and -rs2236225 (p = 0.006) in predicting Hcy levels. The association between 6W-EDR and Hcy levels was found only in subjects within lower 25(OH)D quartiles (<33.26 ng/mL), with the association between 4M-EDR and Hcy occurring only in subjects carrying the -rs2236225 variant. 4M-EDR, 6W-EDR, and -rs2236225 were also independent predictors of Hcy. Findings highlight nutrient-environment and gene-environment interactions that could influence the risk of Hcy-related outcomes.
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http://dx.doi.org/10.3390/nu12051455DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7284830PMC
May 2020

Encapsulation of phenolic-rich extract from banana ( cavendish) peel.

J Food Sci Technol 2020 Jun 9;57(6):2089-2098. Epub 2020 Jan 9.

1School of Environmental and Life Sciences, University of Newcastle, 10 Chittaway Road, Ourimbah, NSW 2258 Australia.

Banana peel, a by-product rich in phenolics and other bioactive compounds, has great potentials as a natural preservative or healthy food ingredient. However, the instability of bioactive compounds derived from banana peel limits their applications, and as such encapsulation is necessary to improve their stability and widen their applications. This study investigated the impact of spray drying conditions and coating materials on the physical, phytochemical, and antioxidant properties of the peel extract to identify the most suitable encapsulation process. The results showed that inlet temperature (ranging from 140 to 180 °C) and feeding rate (3-15 mL/min) did not significantly affect the total phenolic content (TPC) and antioxidant capacity but influenced the moisture content and recovery yield of the powder. The ratio of dry matter in fresh extract-to-coating material (DM-to-CM) (1:1-1:7 (w/w)) did not affect the moisture content. However, it affected the TPC, antioxidant properties, and recovery yield of the powder. Finally, the type of coating materials did not significantly affect TPC and antioxidant properties, but other physical properties, dopamine levels and recovery yield. The most suitable encapsulation conditions were identified as an inlet drying temperature of 150 °C, a feeding rate of 9 mL/min, a ratio of DM-to-CM of 1:1 (w/w), and coating with a combination of maltodextrin M100 and gum acacia. Powder prepared under the most suitable conditions had a spherical shape with a rough surface and had stable TPC under storage conditions of 40 °C for 4 weeks. It also has ideal physical, phytochemical and antioxidant properties and is suitable for further applications.
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http://dx.doi.org/10.1007/s13197-020-04243-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7230113PMC
June 2020

Tetraspanin CD9 is Regulated by miR-518f-5p and Functions in Breast Cell Migration and In Vivo Tumor Growth.

Cancers (Basel) 2020 Mar 26;12(4). Epub 2020 Mar 26.

School of Biomedical Science and Pharmacy, The University of Newcastle and Hunter Medical Research Institute (HMRI), Newcastle, NSW 2308, Australia.

Breast cancer is the most commonly diagnosed and the second leading cause of cancer-related mortality among women worldwide. miR-518f-5p has been shown to modulate the expression of the metastasis suppressor CD9 in prostate cancer. However, the role of miR-518f-5p and CD9 in breast cancer is unknown. Therefore, this study aimed to elucidate the role of miR-518f-5p and the mechanisms responsible for decreased CD9 expression in breast cancer, as well as the role of CD9 in de novo tumor formation and metastasis. miR-518f-5p function was assessed using migration, adhesion, and proliferation assays. miR-518f-5p was overexpressed in breast cancer cell lines that displayed significantly lower CD9 expression as well as less endogenous CD9 3'UTR activity, as assessed using qPCR and dual luciferase assays. Transfection of miR-518f-5p significantly decreased CD9 protein expression and increased breast cell migration in vitro. Cd9 deletion in the MMTV/PyMT mouse model impaired tumor growth, but had no effect on tumor initiation or metastasis. Therefore, inhibition of miR-518f-5p may restore CD9 expression and aid in the treatment of breast cancer metastasis.
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http://dx.doi.org/10.3390/cancers12040795DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226392PMC
March 2020

Environmental UVR Levels and Skin Pigmentation Gene Variants Associated with Folate and Homocysteine Levels in an Elderly Cohort.

Int J Environ Res Public Health 2020 02 28;17(5). Epub 2020 Feb 28.

School of Environmental & Life Sciences, University of Newcastle, Ourimbah, NSW 2258, Australia.

Ultraviolet radiation (UVR) is a ubiquitous exposure which may contribute to decreased folate levels. Skin pigmentation mediates the biological effect of UVR exposure, but its relationship to folate levels is unexamined. Interactions may exist between UVR and pigmentation genes in determining folate status, which may, in turn, impact homocysteine levels, a potential risk factor for multiple chronic diseases. Therefore, independent and interactive influences of environmental UVR and genetic variants related to skin pigmentation (MC1R-rs1805007, IRF4-rs12203592 and HERC2-rs12913832) on folate (red blood cell (RBC) and serum) and homocysteine levels were examined in an elderly Australian cohort (n = 599). Genotypes were assessed by RT/RFLP-PCR, and UVR exposures were assessed as the accumulated erythemal dose rate accumulated over 4 months (4M-EDR). Multivariate analysis found significant negative associations between 4M-EDR and RBC folate (p < 0.001, β = -0.19), serum folate (p = 0.045, β = -0.08) and homocysteine levels (p < 0.001, β = -0.28). Significant associations between -rs1805007 and serum folate levels ( = 0.020), and -rs12203592 and homocysteine levels ( = 0.026) occurred but did not remain significant following corrections with confounders. No interactions between 4M-EDR and pigmentation variants in predicting folate/homocysteine levels were found. UVR levels and skin pigmentation-related variants are potential determinants of folate and homocysteine status, although, associations are mixed and complex, with further studies warranted.
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http://dx.doi.org/10.3390/ijerph17051545DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7084217PMC
February 2020

Elaeocarpus reticulatus fruit extracts reduce viability and induce apoptosis in pancreatic cancer cells in vitro.

Mol Biol Rep 2020 Mar 17;47(3):2073-2084. Epub 2020 Feb 17.

School of Environmental and Life Sciences, University of Newcastle, Ourimbah, 2258, Australia.

Treatment options for pancreatic cancer (PC) are severely limited due to late diagnosis, early metastasis and the inadequacy of chemotherapy and radiotherapy to combat the aggressive biology of the disease. In recent years, plant-derived bioactive compounds have emerged as a source of novel, anti-cancer agents. Used in traditional medicine worldwide, Elaeocarpus species have reported anti-inflammatory, antioxidant and anti-cancer properties. This study aimed to isolate and identify potential anti-PC compounds in the fruit of Elaeocarpus reticulatus Sm. A 50% acetone crude extract significantly decreased the viability of four pancreatic cell lines (≥ 10 µg/mL for BxPC-3 cells) and induced apoptosis in BxPC-3 and HPDE cells. Analysis by HPLC identified the triterpenoid Cucurbitacin I as a likely component of the extract. Furthermore, treatment with Cucurbitacin I significantly reduced the viability of HPDE and BxPC-3 cells, with results comparable to the same concentration of gemcitabine. Interestingly, attempts to isolate bioactive compounds revealed that the crude extract was more effective at reducing PC-cell viability than the fractionated extracts. This study provides initial insight into the bioactive constituents of E. reticulatus fruits.
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http://dx.doi.org/10.1007/s11033-020-05307-8DOI Listing
March 2020

In vitro anti-pancreatic cancer activity of HPLC-derived fractions from Helicteres hirsuta Lour. stem.

Mol Biol Rep 2020 Feb 14;47(2):897-905. Epub 2019 Nov 14.

School of Environmental and Life Sciences, Faculty of Science, University of Newcastle, Brush Road, Ourimbah, NSW, 2258, Australia.

Pancreatic cancer (PC) is one of the leading causes of cancer death in Western societies. The absence of specific symptoms, late diagnosis and the resistance towards chemotherapy result in significant treatment difficulties. As such, it is important to find more effective therapeutic agents for the treatment of PC. Helicteres hirsuta Lour. (H. hirsuta) has been traditionally used in many countries for the treatment of various ailments, indicating that it contains potential therapeutic agents. This study aimed to derive different fractions from the saponin-enriched extract of H. hirsuta stem using RP-HPLC and examine the in vitro anti-pancreatic cancer activity of the derived fractions (F0-F5). With the exception of F0, the five fractions (F1-F5) possessed strong inhibitory activity against PC cells at IC values of 3.11-17.12 μg/mL. The flow cytometry assays revealed the active fractions caused cell cycle arrest at S phase and promoted apoptosis in MIAPaCa-2 PC cells. The LC/MS analysis revealed that the isolated fractions contained bioactive compounds, such as caffeic acid, rosmarinic acid, sagerinic acid, usnic acid, cucurbitacins and absinthin. It can be concluded that the fractions isolated from H. hirsuta stem exhibit potent in vitro anti-pancreatic cancer activity and thus warrant further in vivo studies to assess their activity against PC followed by isolation of individual bioactive compounds and the evaluation of their anti-pancreatic cancer activity.
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http://dx.doi.org/10.1007/s11033-019-05180-0DOI Listing
February 2020

Improving the storage quality of Tahitian limes () by pre-storage UV-C irradiation.

J Food Sci Technol 2019 Mar 18;56(3):1438-1444. Epub 2019 Feb 18.

1School of Environmental and Life Sciences, University of Newcastle, PO Box 127, Ourimbah, NSW 2258 Australia.

UV-C (180-280 nm) has been shown to extend the postharvest shelf-life of many horticulture crops. In this study, Tahitian limes () were exposed to 0, 3.4, 7.2 and 10.5 kJ m UV-C then stored for 28 days in air at 10 °C and 80% RH. Weight loss, peel colour, calyx abscission, ethylene production, respiration rate, total soluble solids (TSS), titratable acidity (TA) and acceptability index were assessed. The results showed that UV-C treatment maintained lime peel green colour and retained calyx attachment after 28 days storage. UV-C treatment also affected endogenous ethylene production and respiration rate, where the highest UV-C treatment (10.5 kJ m) maintained low ethylene production and low respiration rates after 28 days storage with no differences between the different UV-C intensities. In terms of fruit acceptability, limes were exposed to 10.5 kJ m UV-C had a 60% acceptability index after 28 days storage, while untreated control fruit retained acceptability of 39%. In general, the pre-storage UV-C treatments did not affect fruit weight loss, TSS or TA contents during storage.
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http://dx.doi.org/10.1007/s13197-019-03623-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6423171PMC
March 2019

Maximising recovery of phenolic compounds and antioxidant properties from banana peel using microwave assisted extraction and water.

J Food Sci Technol 2019 Mar 19;56(3):1360-1370. Epub 2019 Feb 19.

1School of Environmental and Life Sciences, University of Newcastle, 10 Chittaway Road, Ourimbah, NSW 2258 Australia.

Banana peel is rich in phenolic compounds and is generally considered as waste. This study aimed to maximise recovery of phenolics from banana peel using water via microwave assisted extraction. The impact of various parameters including pH of solvent, sample to solvent ratio, irradiation time with/without cooling periods, and irradiation power were investigated individually. Following this, extraction conditions were further optimised using Response Surface Methodology. The results revealed that the extraction efficiency can be significantly improved by reducing the pH of water, increasing microwave power and time. However, cooling time during irradiation did not affect the extraction efficiency. Optimal conditions were identified at pH of 1, ratio of 2:100 g/mL, 6 min irradiation, and microwave power of 960 W. Under these optimal conditions, approximately 50.55 mg phenolics could be recovered from 1 g dried peel. These conditions are recommended for recovery of phenolic compounds from banana peel for further utilisation.
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http://dx.doi.org/10.1007/s13197-019-03610-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6423337PMC
March 2019

Phytochemical, antioxidant, anti-proliferative and antimicrobial properties of Catharanthus roseus root extract, saponin-enriched and aqueous fractions.

Mol Biol Rep 2019 Jun 3;46(3):3265-3273. Epub 2019 Apr 3.

School of Environmental and Life Sciences, Faculty of Science, University of Newcastle, Brush Road, Ourimbah, NSW, 2258, Australia.

Catharanthus roseus (L.) G. Don (C. roseus) is a well-known medicinal plant for its source of alkaloids solely found in the leaves. Other parts including the root are usually discarded after the alkaloid extraction. This study sought to investigate phytochemical profiles, antioxidant, antimicrobial and cytotoxic properties of the C. roseus root extract (RE) and its two sub-fractions including saponin-enriched (SE) and aqueous (AQ) fractions. The results showed that the RE was a rich source of saponins (1744.44 mg ESE/g) and phenolics (51.27 mg GAE/g), which comprised of gallic acid (25.74 mg/g), apigenin (1.45 mg/g) and kaempferol (1.58 mg/g). The SE fraction was enriched with 31% of saponins and 63% of phenolics higher than those of the RE; whereas the concentrations of saponins and phenolics of the AQ fraction were lower than those of the RE by 40% and 74%, respectively. The content of gallic acid in the SE fraction was 1.4-fold and 1.5-fold higher than those of the RE or AQ fraction, respectively. The SE fraction demonstrated potent antioxidant capacity, which was significantly higher than the RE or AQ fraction, and also exhibited strong anti-proliferative activity against 11 cancer cell lines including A2780 (ovarian), H460 (lung), A431 (skin), MIA PaCa-2 (pancreas), Du145 (prostate), HT29 (colon), MCF-7 (breast), BE2-C (neuroblastoma), SJ-G2, U87 and SMA (glioblastoma) with low GI values (≤ 2.00 µg/mL). The SE fraction was also shown to effectively inhibit the growth of both bacteria (Escherichia coli, Enterobacter aerogenes and Staphylococccus lugdunensis) and fungi (Candida albicans and Aspergillus niger). These findings warrant further investigation to isolate major compounds from the SE fraction and further test their antioxidant, anticancer and antimicrobial activities.
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http://dx.doi.org/10.1007/s11033-019-04786-8DOI Listing
June 2019

Starch-based films: Major factors affecting their properties.

Int J Biol Macromol 2019 Jul 26;132:1079-1089. Epub 2019 Mar 26.

School of Environmental and Life Sciences, University of Newcastle, Ourimbah, NSW 2258, Australia. Electronic address:

Starch is the most popular plant polysaccharides, which has been widely used for the development of edible coating films because of its abundance, cost-effectiveness, and excellent film-forming abilities. Starch-based films have good optical, organoleptic and gas barrier properties, however, they have poor mechanical properties. Many attempts have been made to overcome these limitations, such as the addition of co-biopolymers or other secondary additives to improve the mechanical and tensile properties of the films. Properties of the starch-based films can be influenced by many factors, including types of starches, temperature and time during film formation, plasticizers, co-biopolymers, and storage conditions. Understanding the mechanisms of these factors is very important for future studies on the development of starch-based films. This review focuses on starch as a film/coating material and comprehensively discusses the effects of major factors on properties of starch-based films.
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http://dx.doi.org/10.1016/j.ijbiomac.2019.03.190DOI Listing
July 2019

Cytotoxic activity of extracts and fractions from root and against pancreatic cancer cell lines.

J Cancer Res Ther 2019 Jan-Mar;15(1):245-249

School of Environmental and Life Sciences, Faculty of Science, University of Newcastle, Ourimbah, NSW 2258, Australia.

Objective: The aim of this study was to assess cytotoxic activity of extracts and fractions from the Paramignya trimera root (PTR) and Phyllanthus amarus (PA) against two pancreatic cancer cell lines (primary: BxPc3 and secondary: CFPAC1).

Materials And Methods: The root of PT and whole plant of PA were used in this study. The extracts and fractions from the PTR and PA were prepared using microwave-assisted extraction and high-performance liquid chromatography, respectively. The cytotoxic activity was assessed using the Dojindo Cell Counting Kit-8 assay.

Results: The findings showed impressive cytotoxic capacity of the PTR extract against both pancreatic cancer cells of BxPc3 and CFPAC1 in a range of concentrations from 50 to 200 μg/mL, which was higher than those of ostruthin (67 μM), gemcitabine (50 nM), and four its fractions (50 μg/mL), and to be comparable to a saponin-enriched extract from Quillaja bark at 200 μg/mL. In contrast, the cytotoxic capacity of the PA extract and nine its fractions against these pancreatic cancer cell lines was significantly lower (P < 0.05) than those of gemcitabine (50 nM) and Quillaja bark extract (200 μg/mL) and being comparable to phyllanthin (4.8 μM). The IC values of the PTR extract against BxPc3 and CFPAC1 cancer cells were 32.12 and 36.65 μg/mL, respectively, which was much lower than that of the PA extract against CFPAC1 cancer cells (128.81 μg/mL).

Conclusion: The outcomes obtained from this study reveal that the PTR extract is a lead source for the potential development of novel antipancreatic cancer drugs and/or functional foods.
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http://dx.doi.org/10.4103/jcrt.JCRT_85_18DOI Listing
July 2019

The Bispidinone Derivative 3,7-Bis-[2-()-amino-3-(1-indol-3-yl)-propionyl]-1,5-diphenyl-3,7-diazabicyclo[3.3.1]nonan-9-one Dihydrochloride Induces an Apoptosis-Mediated Cytotoxic Effect on Pancreatic Cancer Cells In Vitro.

Molecules 2019 Jan 31;24(3). Epub 2019 Jan 31.

Pancreatic Cancer Research Group, School of Environmental and Life Sciences, The University of Newcastle, Ourimbah, NSW 2258, Australia.

Pancreatic cancer (PC) is a complex, heterogeneous disease with a dismal prognosis. Current therapies have failed to improve survival outcomes, urging the need for discovery of novel targeted treatments. Bispidinone derivatives have yet to be investigated as cytotoxic agents against PC cells. The cytotoxic effect of four bispidinone derivatives (: 1,5-diphenyl-3,7-bis(2-hydroxyethyl)-3,7-diazabicyclo[3.3.1]nonan-9-one; : 3,7-bis-(2-(S)-amino-4-methylsulfanylbutyryl)-1,5-diphenyl-3,7-diazabicyclo[3.3.1]nonan-9-one dihydrochloride; [2-{7-[2-()--butoxycarbonylamino-3-(1-indol-3-yl)-propionyl]-9-oxo-1,5-diphenyl-3,7-diazabicyclo[3.3.1]non-3-yl}-1-()-(1-indol-3-ylmethyl)-2-oxoethyl]-carbamic acid tertbutyl ester; : 3,7-bis-[2-()-amino-3-(1-indol-3-yl)-propionyl]-1,5-diphenyl-3,7-diazabicyclo[3.3.1]nonan-9-one dihydrochloride) was assessed against PC cell lines (MiaPaca-2, CFPAC-1 and BxPC-3). Cell viability was assessed using a Cell Counting Kit-8 (CCK-8) colorimetric assay, while apoptotic cell death was confirmed using fluorescence microscopy and flow cytometry. Initial viability screening revealed significant cytotoxic activity from treatment (1 µM⁻100 µM) on all three cell lines, with IC values for MiaPaca-2, BxPC-3, and CFPAC-1 16.9 µM, 23.7 µM, and 36.3 µM, respectively. Cytotoxic treatment time-response (4 h, 24 h, and 48 h) revealed a 24 h treatment time was sufficient to produce a cytotoxic effect on all cell lines. Light microscopy evaluation (DAPI staining) of treated MiaPaca-2 PC cells revealed dose-dependent characteristic apoptotic morphological changes. In addition, flow cytometry confirmed induced apoptotic cell death induction of activated caspase-3/-7. The bispidinone derivative induced an apoptosis-mediated cytotoxic effect on MiaPaca-2 cell lines and significant cytotoxicity on CFPAC-1 and BxPC-3 cell lines. Further investigations into the precise cellular mechanisms of action of this class of compounds are necessary for potential development into pre-clinical trials.
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http://dx.doi.org/10.3390/molecules24030524DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6384835PMC
January 2019

Comparative cytotoxic activity between kaempferol and gallic acid against various cancer cell lines.

Data Brief 2018 Dec 27;21:1033-1036. Epub 2018 Oct 27.

School of Environmental and Life Sciences, Faculty of Science, University of Newcastle, Ourimbah, NSW 2258, Australia.

This data article indicates the cytotoxicity of kaempferol and gallic acid across different cancer cell lines including A2780 (ovarian), H460 (lung), A431 (skin), MIA PaCa-2 (pancreas), Du145 (prostate), HT29 (colon), MCF-7 (breast), BE2-C (neuroblastoma), SJ-G2, U87 and SMA (glioblastoma). The dataset showed that the inhibitory activity of kaempferol was comparatively stronger than gallic acid. Thereby, kaempferol is offered as a potent anticancer agent for further investigation and beneficial as a dietary supplement. The data within this article relates to the research article entitled "Screening phytochemical content, antioxidant, antimicrobial and cytotoxic activities of (L.) G. Don stem extract and its fractions" (Pham et al., 2018).
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http://dx.doi.org/10.1016/j.dib.2018.10.121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6226582PMC
December 2018

In vitro antibacterial and anticancer properties of Helicteres hirsuta Lour. leaf and stem extracts and their fractions.

Mol Biol Rep 2018 Dec 12;45(6):2125-2133. Epub 2018 Sep 12.

School of Environmental and Life Sciences, Faculty of Science, University of Newcastle, Brush Road, Ourimbah, NSW, 2258, Australia.

Helicteres hirsuta Lour. (H. hirsuta) has been considered as a herbal medicine for the treatment of malaria and diabetes but limited studies have been conducted on its anticancer and antibacterial properties. In this study, the in vitro antibacterial and anticancer properties of the leaf and stem extracts and their two sub-fractions (aqueous and saponin-enriched butanol fractions) prepared from H. hirsuta were elucidated. MTT and CCK-8 assays were employed to assess their in vitro anticancer properties against various cancer cell lines. The antibacterial activity was assessed using the disc diffusion method and minimum inhibitory concentration (MIC) values were determined. The results revealed that the saponin-enriched fractions from H. hirsuta leaves and stems showed the highest antibacterial activity against E. coli (MIC values of 2.50 and 5.00 mg/mL, respectively) and S. lugdunensis (MIC values of 0.35 and 0.50 mg/mL, respectively). Importantly, these saponin-enriched fractions possessed strong anticancer activity in vitro towards a range of cancer cell lines including MIA PaCa-2 (pancreas); A2780 (ovarian); H460 (lung); A431 (skin); Du145 (prostate); HT29 (colon); MCF-7 (breast); SJ-G2, U87, SMA (glioblastoma) and BE2-C (neuroblastoma) at low doses (GI values of 0.36-11.17 µg/mL). They especially revealed potent anti-pancreatic cancer activity in vitro against MIA PaCa-2, BxPC-3 and CFPAC-1 cells with IC values of 1.80-6.43 µg/mL. This finding provides scientific evidence of the cytotoxic activity of the extracts prepared from H. hirsuta leaves and stems, and suggests further studies to isolate active compounds for development of new anticancer agents from these plant extracts.
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http://dx.doi.org/10.1007/s11033-018-4370-xDOI Listing
December 2018

Lipidomic profiling of extracellular vesicles derived from prostate and prostate cancer cell lines.

Lipids Health Dis 2018 Sep 8;17(1):211. Epub 2018 Sep 8.

School of Biomedical Sciences and Pharmacy, University of Newcastle, Ourimbah, NSW, Australia.

Background: Extracellular vesicles (EVs) are produced and secreted from most cells of the body and can be recovered in biological fluids. Although there has been extensive characterisation of the protein and nucleic acid component of EVs, their lipidome has received little attention and may represent a unique and untapped source of biomarkers for prostate cancer diagnosis and prognosis.

Methods: EVs were isolated from non-tumourigenic (RWPE1), tumourigenic (NB26) and metastatic (PC-3) prostate cell lines. Lipids were extracted and subsequently used for targeted lipidomics analysis for the quantitation of molecular lipid species.

Results: A total of 187 molecular lipid species were quantitatively identified in EV samples showing differential abundance between RWPE1, NB26 and PC-3 EV samples. Fatty acids, glycerolipids and prenol lipids were more highly abundant in EVs from non-tumourigenic cells, whereas sterol lipids, sphingolipids and glycerophospholipids were more highly abundant in EVs from tumourigenic or metastatic cells.

Conclusions: This study identified differences in the molecular lipid species of prostate cell-derived EVs, increasing our understanding of the changes that occur to the EV lipidome during prostate cancer progression. These differences highlight the importance of characterising the EV lipidome, which may lead to improved diagnostic and prognostic biomarkers for prostate cancer.
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http://dx.doi.org/10.1186/s12944-018-0854-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6128989PMC
September 2018

Combined postharvest UV-C and 1-methylcyclopropene (1-MCP) treatment, followed by storage continuously in low level of ethylene atmosphere improves the quality of Tahitian limes.

J Food Sci Technol 2018 Jul 27;55(7):2467-2475. Epub 2018 Apr 27.

1School of Environmental and Life Sciences, University of Newcastle, PO Box 127, Ourimbah, NSW 2258 Australia.

The green Tahitian limes () were exposed to 7.2 kJ m UV-C and 0.5 μL L 1-methylcyclopropene (1-MCP) treatments both separately and in combination. After treatment, fruit were stored in ethylene free (i.e. air containing < 0.005 μL L) or 0.1 μL L ethylene at 20 °C and 100% RH. The results showed that UV-C treatment delayed skin degreening and reduced endogenous ethylene production compared to untreated control fruit, however these effects reduced over the storage time. As expected, 1-MCP inhibited ethylene production, reduced calyx abscission and retained peel greenness during the storage. Both of the combination treatments, 1-MCP + UV-C and UV-C + 1-MCP reduced endogenous ethylene production and delayed skin yellowing. In all treatments, UV-C and 1-MCP resulted in lower fruit respiration rates than untreated control fruit, however this effect diminished during 7 and 14 days storage for fruits stored in air and 0.1 μL L ethylene atmosphere, respectively. There was no difference in weight loss, SSC, TA and SSC/TA ratio between the treatments and storage conditions. The results suggest that a pre-storage UV-C treatment, followed by storage at low level of ethylene improves the quality of limes, with the additional improvement when combined with 1-MCP treatment prior or after UV-C irradiation.
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http://dx.doi.org/10.1007/s13197-018-3164-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6033800PMC
July 2018

Encapsulation of Citrus By-Product Extracts by Spray-Drying and Freeze-Drying Using Combinations of Maltodextrin with Soybean Protein and ι-Carrageenan.

Foods 2018 Jul 19;7(7). Epub 2018 Jul 19.

School of Environmental and Life Sciences, The University of Newcastle, P.O. Box 127, Ourimbah, NSW 2258, Australia.

The effect of different combinations of maltodextrin (MD) coating agents (MD, MD + soybean protein, and MD + ι-carrageenan) on the encapsulation of lemon by-product aqueous extracts using freeze-drying and spray-drying were investigated. The total phenolic content (TPC), total flavonoid content (TFC), and ferric ion reducing antioxidant power (FRAP) of the microparticles were evaluated. Freeze-drying with the mixture of MD + soybean protein resulted in the highest retention of TPC, TFC, and FRAP (1.66 ± 0.02 mg GAE/g d.b., 0.43 ± 0.02 mg CE/g d.b., and 3.70 ± 0.05 mM TE/g, respectively). Freeze-drying resulted in microparticles with lower moisture content (MC) and water activity (a) than those produced by spray-drying. Specifically, the MC and a of the microparticles produced by freeze-drying ranged from 1.15 to 2.15% and 0.13 to 0.14, respectively, while the MC and a of the microparticles produced by spray-drying ranged from 6.06% to 6.60% and 0.33 to 0.40, respectively. Scanning electron microscopy revealed that spray-drying resulted in the formation of spherical particles of different sizes regardless of the type of coating agent. Although freeze-drying resulted in microparticles with amorphous glassy shapes, the mixture of MD + soybean protein resulted in the formation of spherical porous particles. X-ray diffraction revealed a low degree of crystallinity for the samples produced by both techniques.
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http://dx.doi.org/10.3390/foods7070115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6069085PMC
July 2018

The Olive Biophenols Oleuropein and Hydroxytyrosol Selectively Reduce Proliferation, Influence the Cell Cycle, and Induce Apoptosis in Pancreatic Cancer Cells.

Int J Mol Sci 2018 Jul 2;19(7). Epub 2018 Jul 2.

Pancreatic Cancer Research Group, School of Environmental & Life Sciences, University of Newcastle, Ourimbah 2258, NSW, Australia.

Current chemotherapy drugs for pancreatic cancer only offer an increase in survival of up to six months. Additionally, they are highly toxic to normal tissues, drastically affecting the quality of life of patients. Therefore, the search for novel agents, which induce apoptosis in cancer cells while displaying limited toxicity towards normal cells, is paramount. The olive biophenols, oleuropein, hydroxytyrosol and tyrosol, have displayed cytotoxicity towards cancer cells without affecting non-tumorigenic cells in cancers of the breast and prostate. However, their activity in pancreatic cancer has not been investigated. Therefore, the aim of this study was to determine the anti-pancreatic cancer potential of oleuropein, hydroxytyrosol and tyrosol. Pancreatic cancer cells (MIA PaCa-2, BxPC-3, and CFPAC-1) and non-tumorigenic pancreas cells (HPDE) were treated with oleuropein, hydroxytyrosol and tyrosol to determine their effect on cell viability. Oleuropein displayed selective toxicity towards MIA PaCa-2 cells and hydroxytyrosol towards MIA PaCa-2 and HPDE cells. Subsequent analysis of Bcl-2 family proteins and caspase 3/7 activation determined that oleuropein and hydroxytyrosol induced apoptosis in MIA PaCa-2 cells, while oleuropein displayed a protective effect on HPDE cells. Gene expression analysis revealed putative mechanisms of action, which suggested that c-Jun and c-Fos are involved in oleuropein and hydroxytyrosol induced apoptosis of MIA PaCa-2 cells.
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http://dx.doi.org/10.3390/ijms19071937DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6073890PMC
July 2018

An Array of Bioactive Compounds From Australian Eucalypts and Their Relevance in Pancreatic Cancer Therapeutics.

Pancreas 2018 07;47(6):690-707

School of Environmental and Life Sciences, Faculty of Science, University of Newcastle, Ourimbah, NSW, Australia.

Pancreatic cancer (PC) is one of the most devastating human cancers, and despite the significant advances in the current therapeutic options, the overall survival rate for PC has remained static for the past 50 years. Plant-derived bioactive compounds play a vital role in cancer therapeutics by providing new lead compounds for future drug development. Therefore, the isolation, characterization, and identification of new bioactive compounds for the prevention and treatment of cancer continue to be an important aspect of natural product research. Many in vitro and in vivo studies published in the last few decades have established strong links between the phytochemical profile of eucalypts and anticancer activity. However, only a small number of these reports have attempted to demonstrate a relationship between the biological activity of eucalypt extracts and PC. This review focuses on potential anti-PC effects of an array of bioactive compounds present in various species of eucalypts. It also highlights the necessity for further in vitro and in vivo studies to develop a complete understanding of the potential this group of plants has for the development of potent and specific chemotherapeutic drugs for PC.
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http://dx.doi.org/10.1097/MPA.0000000000001074DOI Listing
July 2018

Extracellular vesicles with altered tetraspanin CD9 and CD151 levels confer increased prostate cell motility and invasion.

Sci Rep 2018 06 11;8(1):8822. Epub 2018 Jun 11.

Cancer Research Program, Hunter Medical Research Institute, New Lambton, NSW, Australia.

To facilitate intercellular communication, cells release nano-sized, extracellular vesicles (EVs) to transfer biological cargo to both local and distant sites. EVs are enriched in tetraspanins, two of which (CD9 and CD151) have altered expression patterns in many solid tumours, including prostate cancer, as they advance toward metastasis. We aimed to determine whether EVs from prostate cells with altered CD9 and CD151 expression could influence cellular behaviour and increase the metastatic capabilities of non-tumourigenic prostate cells. EVs were isolated by ultrafiltration and characterised for their tetraspanin expression and size distribution. iTRAQ was used to identify differences between RWPE1 and tetraspanin-modified RWPE1 EV proteomes, showing an enrichment in protein degradation pathways. Addition of EVs from RWPE1 cells with reduced CD9 or increased CD151 abundance resulted in increased invasion of RWPE1 cells, and increased migration in the case of high CD151 abundance. We have been able to show that alteration of CD9 and CD151 on prostate cells alters the proteome of their resultant EVs, and that these EVs can enhance the migratory and invasive capabilities of a non-tumourigenic prostate cellular population. This work suggests that cellular tetraspanin levels can alter EVs, potentially acting as a driver of metastasis in prostate cancer.
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http://dx.doi.org/10.1038/s41598-018-27180-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5995928PMC
June 2018
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