Publications by authors named "Mohammad Y Alshahrani"

12 Publications

  • Page 1 of 1

Synergistic Effect of Plant Extracts on Endodontic Pathogens Isolated from Teeth with Root Canal Treatment Failure: An In Vitro Study.

Antibiotics (Basel) 2021 May 9;10(5). Epub 2021 May 9.

Department of Restorative Dental Sciences, College of Dentistry, King Khalid University, Abha 61321, Saudi Arabia.

Background And Objectives: This study aimed to evaluate the synergistic antimicrobial activity of extracts obtained from (Miswak), (myrrh) and (neem) in combination with commercially available antimicrobial agents: penicillin, tetracycline, ofloxacin and fluconazole on endodontic pathogens such as and .

Materials And Methods: Microbiological samples from the root canals of the teeth undergoing retreatment were taken using sterile paper points kept at full length in the canal for 30 s. The disc diffusion method was used to check the susceptibility of microbes to the plant extracts and antimicrobials by measuring the diameter of the inhibition zones. Against the microbes, minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC)/minimum fungicidal concentration (MFC) of the plant extracts were assessed. The fractional inhibitory concentration index (FICI) was used to estimate the synergistic effect of plant extracts combined with antimicrobials against the resistant endodontic microbes.

Results: The findings clearly indicate the effectiveness of all the three plant extracts, against all the experimental pathogenic microorganisms except for the ineffectiveness of against Maximum antimicrobial activity was displayed by against (MIC = 0.09 ± 1.2 mg/mL, MBC = 0.78 ± 1.25 mg/mL) and the minimum antimicrobial activity was displayed by against (MIC = 12.5 ± 3.25 mg/mL, MBC = 100 ± 3.75 mg/mL). The best synergy was displayed by with fluconazole against (FICI = 0.45).

Conclusions: The current study delineates the variable antimicrobial activity of plant extracts against the experimental endodontic pathogenic microorganisms. Plant extracts in conjunction with various antimicrobials can be valuable aids in combating relatively resistant endodontic microorganisms that have been the cause of worry in recent years, leading to failure even in treatment procedures following all required protocols.
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http://dx.doi.org/10.3390/antibiotics10050552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8151008PMC
May 2021

Antibody profile in symptomatic/asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected Saudi persons.

Saudi J Biol Sci 2021 Aug 3;28(8):4677-4682. Epub 2021 May 3.

Research Center for Advanced Materials Science (RCAMS), King Khalid University, P.O. Box 9004, Abha 61413, Saudi Arabia.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected persons could be symptomatic or asymptomatic. Asymptomatic and symptomatic patients can transmit SARS-CoV-2. This study aimed to study the humoral immune response in Saudis who are Covid-19 symptomatic and asymptomatic patients. We created three types of enzyme-linked immunosorbant assays (ELISAs) to reveal IgG and IgM antibodies (Abs) against SARS-CoV-2. The developed ELISAs were designed to detect Abs against SARS-CoV-2 N, S and N + S proteins. A number of Covid-19 symptomatic (1 5 3) and asymptomatic (84) RT-PCR-confirmed patient sera were used to evaluate the ELISAs and to determine the IgG and IgM antibody profile in those patients. The sensitivity and specificity of these ELISAs were evaluated using pre-Covid-19 pandemic serum samples. The results revealed the existence of anti-SARS-CoV-2 IgG and IgM Abs in Covid-19 symptomatic and asymptomatic Saudi persons. The use of SARS-CoV-2 N and S proteins in the same ELISA greatly increased the detectability of infection. In conclusion, the Covid-19 symptomatic and asymptomatic Saudi persons demonstrated both IgG and IgM antibody profile with higher titer in symptomatic patients. The use of N + S proteins as antibody capture antigens greatly increased the ELISA sensitivity.
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http://dx.doi.org/10.1016/j.sjbs.2021.04.080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8091802PMC
August 2021

Identification of New Proteasome Inhibitors Using a Knowledge-Based Computational Screening Approach.

Molecules 2021 Apr 16;26(8). Epub 2021 Apr 16.

Department of Medical Biotechnology, Yeungnam University, Gyeongsan 38541, Korea.

(Mtb) is a deadly tuberculosis (TB)-causing pathogen. The proteasome is vital to the survival of Mtb and is therefore validated as a potential target for anti-TB therapy. Mtb resistance to existing antibacterial agents has enhanced drastically, becoming a worldwide health issue. Therefore, new potential therapeutic agents need to be developed that can overcome the complications of TB. With this purpose, in the present study, 224,205 natural compounds from the ZINC database have been screened against the catalytic site of Mtb proteasome by the computational approach. The best scoring hits, ZINC3875469, ZINC4076131, and ZINC1883067, demonstrated robust interaction with Mtb proteasome with binding energy values of -7.19, -7.95, and -7.21 kcal/mol for the monomer (K-chain) and -8.05, -9.10, and -7.07 kcal/mol for the dimer (both K and L chains) of the beta subunit, which is relatively higher than that of reference compound HT1171 (-5.83 kcal/mol (monomer) and -5.97 kcal/mol (dimer)). In-depth molecular docking of top-scoring compounds with Mtb proteasome reveals that amino acid residues Thr1, Arg19, Ser20, Thr21, Gln22, Gly23, Asn24, Lys33, Gly47, Asp124, Ala126, Trp129, and Ala180 are crucial in binding. Furthermore, a molecular dynamics study showed steady-state interaction of hit compounds with Mtb proteasome. Computational prediction of physicochemical property assessment showed that these hits are non-toxic and possess good drug-likeness properties. This study proposed that these compounds could be utilized as potential inhibitors of Mtb proteasome to combat TB infection. However, there is a need for further bench work experiments for their validation as inhibitors of Mtb proteasome.
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http://dx.doi.org/10.3390/molecules26082326DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074214PMC
April 2021

C-type lectin receptors MR and DC-SIGN are involved in recognition of hemocyanins, shaping their immunostimulatory effects on human dendritic cells.

Eur J Immunol 2021 Jul 6;51(7):1715-1731. Epub 2021 May 6.

Fundación Ciencia y Tecnología para el Desarrollo (FUCITED), Santiago, Chile.

Hemocyanins are used as immunomodulators in clinical applications because they induce a strong Th1-biased cell-mediated immunity, which has beneficial effects. They are multiligand glycosylated molecules with abundant and complex mannose-rich structures. It remains unclear whether these structures influence hemocyanin-induced immunostimulatory processes in human APCs. We have previously shown that hemocyanin glycans from Concholepas concholepas (CCH), Fissurella latimarginata (FLH), and Megathura crenulata (KLH), participate in their immune recognition and immunogenicity in mice, interacting with murine C-type lectin receptors (CLRs). Here, we studied the interactions of these hemocyanins with two major mannose-binding CLRs on monocyte-derived human DCs: MR (mannose receptor) and DC-SIGN (DC-specific ICAM-3-grabbing nonintegrin). Diverse analyses showed that hemocyanins are internalized by a mannose-sensitive mechanism. This process was calcium dependent. Moreover, hemocyanins colocalized with MR and DC-SIGN, and were partly internalized through clathrin-mediated endocytosis. The hemocyanin-mediated proinflammatory cytokine response was impaired when using deglycosylated FLH and KLH compared to CCH. We further showed that hemocyanins bind to human MR and DC-SIGN in a carbohydrate-dependent manner with affinity constants in the physiological concentration range. Overall, we showed that these three clinically valuable hemocyanins interact with human mannose-sensitive CLRs, initiating an immune response and promoting a Th1 cell-driving potential.
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http://dx.doi.org/10.1002/eji.202149225DOI Listing
July 2021

Synergistic efficacies of thymoquinone and standard antibiotics against multi-drug resistant isolates.

Saudi Med J 2021 Feb;42(2):196-204

From the Department of Clinical Laboratory Sciences, Central Research Laboratory (Dera, Ahmad, Rajagopalan, Al Shahrani, Alshahrani, Alraey, Alamri, Alasmari, Makkawi, Alkhathami, Zaman, Hakami, Alhefzi), College of Applied Medical Sciences, King Khalid University, and From the Department of Clinical Laboratory Sciences, Central Research Laboratory (AlAmri), College of Applied Medical Sciences, and Cancer Research Unit, King Khalid University, Abha; from the Department of Clinical Laboratory Sciences (Saif), College of Applied Medical Sciences, Najran University, Najran; and the Chair of Medical and Molecular Genetics Research, Department of Clinical Laboratory Sciences (Alfhili), College of Applied Medical Sciences, King Saud University, Riyadh, Kingdom of Saudi Arabia.

Objectives: To explore the antibacterial activity of thymoquinone (TQ), a quinone extracted from .

Methods: This study was conducted from May 2019 to March 2020 at the Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia. The antimicrobial activity, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) of TQ were determined using an agar well diffusion method and broth microdilution assays, and the synergistic effect was evaluated using antibiotics in parallel. The disruptive effect of TQ on bacterial cell membranes was determined using scanning electron microscopy. The antivirulence properties of TQ, which include adherence and biofilm formation, were also investigated using adherence and biofilm formation assays, respectively.

Results: Thymoquinone demonstrated bactericidal efficacy against 4/14 bacterial strains, with MIC range of 1.04-8.3 µg/mL and and MBC range of 10.41-66.66 µg/mL. Thymoquinone showed synergism against , (American Type Culture Collection 12228), , and in combination with the tested antibiotics. Thymoquinone inhibited bacterial adhesion by 39%-54%, 48%-68%, and 61%-81% at 0.5 × MIC, 1 × MIC, and 2 × MIC, respectively. The tested bacterial strains significantly inhibited biofilm formation after treatment with various concentrations of TQ for 24 and 48 hours.

Conclusion: The combinatory effect of TQ with antimicrobials should be considered when developing new antimicrobial therapy regimens to overcome multidrug-resistant.
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http://dx.doi.org/10.15537/smj.2021.2.25706DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7989283PMC
February 2021

A report on tick burden and molecular detection of tick-borne pathogens in cattle blood samples collected from four regions in Saudi Arabia.

Ticks Tick Borne Dis 2021 05 13;12(3):101652. Epub 2021 Jan 13.

Institute of Pure and Applied Biology, Bahauddin Zakariya University Multan, 60800, Pakistan. Electronic address:

Babesiosis, theileriosis and anaplasmosis are among the most commonly reported tick-borne diseases in cattle and are associated with significant economic losses. Through the present study the researchers aimed to report the presence of various pathogens that cause babesiosis, theileriosis and anaplasmosis in cattle collected from different provinces in Saudi Arabia and to report their phylogenetic relationship. A total of 362 blood samples of cattle along with ticks that were present on the cattle were collected from four regions (Riyadh, Al-Kharj, Al-Hasa and Al-Qassim) of Saudi Arabia. Blood samples were screened by polymerase chain reaction (PCR) for the presence of various Babesia, Theileria and Anaplasma species by amplification of their 18S rRNA and/or 23S rRNA genes. A total of 541 ticks were collected and identified from the cattle. These included Hyalomma anatolicum, Hyalomma dromedarii, Hyalomma impeltatum, Hyalomma excavatum, Rhipicephalus annulatus and Rhipicephalus turanicus. Regarding tick-borne pathogens, the overall prevalence was 1.9 % (7/362) for Theileria annulata, (2/362) 0.6 % for Theileria and (21/362) 5.8 % for Anaplasma ovis. Four of the cattle were found to be co-infected with more than one pathogen (1.1 %). We did not detect any Babesia species in the blood of the studied cattle. Prevalence of the Theileria and Anaplasma species was highest in cattle that resided in Riyadh, followed by cattle from Al-Hasa and Al-Qassim. Representative amplified partial-gene sequences of T. annulata (GenBank accession numbers MK826137-39) and A. ovis (GenBank acc. no. MK 880224) were submitted to GenBank. The presence of ticks on cattle was found to be associated with a high prevalence of Theileria spp. (P = 0.02) and Anaplasma ovis (P < 0.001). We report novel genotypes of T. annulata and A. ovis from cattle in Saudi Arabia and we recommend that molecular surveys are undertaken throughout the country to address the prevalence and geographical distribution of tick-borne infections for their effective diagnosis and treatment.
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http://dx.doi.org/10.1016/j.ttbdis.2021.101652DOI Listing
May 2021

Increased mRNA expression of key cytokines among suspected cases of Pneumocystis jirovecii infection.

BMC Infect Dis 2021 Jan 7;21(1):28. Epub 2021 Jan 7.

Department of Microbiology and Clinical Parasitology, College of Medicine, King Khalid University, Abha, Saudi Arabia.

Background: Pneumocystis pneumonia (PCP) is a fatal infectious disease caused by Pneumocystis jirovecii (PJP). The major factor relevant to morbidity and mortality seems to be the host inflammatory reaction. The objective of this study was to evaluate the role of IL-2, IL-4, IL-10, and IL-13 cytokine mRNA expression among suspected P. jirovecii infection.

Methods: This was a cross-sectional analytical study undertaken in Aseer region, Saudi Arabia. One hundred suspected PCP cases and 100 healthy controls were included in the study. Basic clinical manifestations, radiological findings, microbiological and immunological findings were extracted from the hospital records from January 2019 to August 2019, Pneumocystis detection was done by immune-fluorescent staining (IFAT, Gomorimethanamine silver staining (GMSS), Giemsa staining, Toluidine blue O (TBO), and Pneumocystis RT-PCR.

Results: Increased more than 5 fold, 3 fold, 4 fold, and 7 fold of IL-2, IL-4, IL-10, and IL-13 mRNA expression were observed in PCP cases compared to controls. Higher expression of IL-2 mRNA was connected with crept, wheezing and chest X-ray findings like central perihilar infiltrate, patchy infiltrate, consolidation, hilar lymphadenopathy, pneumothorax, pleural effusion which showed higher expression compared to counterpart (p< 0.0001). Higher expression of IL-4 mRNA was found to be significantly associated with weight loss (p=0.002), dyspnea (p=0.003), crept (p=0.01), and chest X-ray findings (p< 0.0001). Significantly increased expression of IL-10 mRNA was observed to be associated with weight loss, dyspnea, night sweats, wheezing, and different findings of chest X-ray compared to their counterparts, whereas, IL-13 mRNA was observed in cases with fever. Suspected cases of PCP confirmed positive by IFTA with higher IL-2, IL-4, and IL-10 mRNA expression compared to negative cases. RT-PCR confirmed PCP cases had significantly higher expression of IL-2, IL-4, and IL-10 as well as IL-13 mRNA compared to negative cases. Positive detected cases by GMSS showed higher IL-2, IL-10 mRNA expression, while Giemsa showed only higher IL-4 mRNA expression compared to negative cases.

Conclusion: Confirmed cases of P. jirovecii showed higher IL-2, IL-4, IL-10, and IL-13 mRNA expression comparatively to negative cases. Increased expression of cytokines may be indicative of infection severity and could help in patients' management.
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http://dx.doi.org/10.1186/s12879-020-05729-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7792013PMC
January 2021

Molecular Survey of Vector-Borne Pathogens of Dogs and Cats in Two Regions of Saudi Arabia.

Pathogens 2020 Dec 31;10(1). Epub 2020 Dec 31.

Department of Pathobiology, Faculty of Veterinary Science, Bu-Ali Sina University, Hamedan 6517658978, Iran.

Dogs and cats play an important role as reservoirs of vector-borne pathogens, yet reports of canine and feline vector-borne diseases in Saudi Arabia are scarce. Blood samples were collected from 188 free-roaming dogs and cats in Asir (70 dogs and 44 cats) and Riyadh (74 dogs), Saudi Arabia. The presence of spp., spp., hemotropic spp., spp., and spp. was detected using a multiplex tandem real-time PCR. PCR-positive samples were further examined with specific conventional and real-time PCR followed by sequencing. Dogs from Riyadh tested negative for all pathogens, while 46 out of 70 dogs (65.7%) and 17 out of 44 cats (38.6%) from Asir were positive for at least one pathogen. Positive dogs were infected with (57.1%), (30%), (15.7%), and (1.4%), and cats were infected with (13.6%), Mycoplasma haemominutum (13.6%), (9.2%), and (2.27%), all of which are reported for the first time in Saudi Arabia. Co-infection with and was detected in 17 dogs (24.28%), while coinfections were not detected in cats. These results suggest that effective control and public awareness strategies for minimizing infection in animals are necessary.
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http://dx.doi.org/10.3390/pathogens10010025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823254PMC
December 2020

Evaluation of antibacterial properties of on clinical isolates of periodontitis patients with special reference to red complex bacteria.

Saudi Pharm J 2020 Oct 17;28(10):1203-1209. Epub 2020 Aug 17.

Department of Pharmaceutics, Era College of Pahrmacy, Era University, Lucknow, UP, India.

Background: Chronic periodontitis has an interplay between different species of bacteria found in dental biofilms act a crucial role in pathogenesis and disease progression. The existing antibacterial therapy is inadequate, associated with many side effects as well as evolving multidrug resistance. Hence, novel drugs development with minimum or no toxicity is an immediate priority.

Methods: Antibacterial efficacy of ethanolic extract of was tested against clinical isolates, ie. and from the patients with chronic periodontitis. Zone of inhibition, the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) were investigated by well diffusion method and micro broth dilution assay using alamar blue. Anti-virulence properties of the extract, which include adherence property and the biofilm formation, were investigated by adherence as well as biofilm formation assay.

Results: extract showed potent inhibitory effect against pathogenic periodontal bacteria with the significant inhibitory zone (13-23 mm), MIC (0.39-1.56 mg/ml) as well as MBC (1.56-6.25 mg/ml). The extract was able to inhibit bacterial adhesion ranged from 30 to 45%, 35 to 63% and 55 to 80% of MIC at MIC × 0.5, MIC × 1 and MIC × 2 respectively. Significant inhibition was found in biofilm formation to all the tested periodontal bacterial strains after the treatment with various concentrations of extract for 24 and 48hrs.

Conclusion: These results reveal for the first time that the extract might be the source of various compounds to be applied for chronic periodontitis therapy, which might draw these valuable compounds to the subsequent phase of development of the drug.
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http://dx.doi.org/10.1016/j.jsps.2020.08.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7584800PMC
October 2020

Cystic Fibrosis: Overview of the Current Development Trends and Innovative Therapeutic Strategies.

Pharmaceutics 2020 Jul 2;12(7). Epub 2020 Jul 2.

National Centre for Pharmaceutical Technology, King Abdulaziz City for Science and Technology (KACST), P.O. Box 6086, Riyadh 11442, Saudi Arabia.

Cystic Fibrosis (CF), an autosomal recessive genetic disease, is caused by a mutation in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). This mutation reduces the release of chloride ions (Cl) in epithelial tissues, and hyperactivates the epithelial sodium channels (ENaC) which aid in the absorption of sodium ions (Na). Consequently, the mucus becomes dehydrated and thickened, making it a suitable medium for microbial growth. CF causes several chronic lung complications like thickened mucus, bacterial infection and inflammation, progressive loss of lung function, and ultimately, death. Until recently, the standard of clinical care in CF treatment had focused on preventing and treating the disease complications. In this review, we have summarized the current knowledge on CF pathogenesis and provided an outlook on the current therapeutic approaches relevant to CF (i.e., CFTR modulators and ENaC inhibitors). The enormous potential in targeting bacterial biofilms using antibiofilm peptides, and the innovative therapeutic strategies in using the CRISPR/Cas approach as a gene-editing tool to repair the CFTR mutation have been reviewed. Finally, we have discussed the wide range of drug delivery systems available, particularly non-viral vectors, and the optimal properties of nanocarriers which are essential for successful drug delivery to the lungs.
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http://dx.doi.org/10.3390/pharmaceutics12070616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7407299PMC
July 2020

detection and comparison of multiple diagnostic methods with quantitative real-time PCR in patients with respiratory symptoms.

Saudi J Biol Sci 2020 Jun 23;27(6):1423-1427. Epub 2020 Apr 23.

Department of Microbiology, Lady Hardinge Medical College, New Delhi, India.

(PCP) remains a significant cause of mortality and morbidity in patients with respiratory infections. Accurate diagnosis of PCP is still a diagnostic challenge. Hence, the main objectives were to study the incidence of pneumonia infection among respiratory problems patients and to compare the real-time quantitative PCR technique with various diagnostic methodologies. Patients who have respiratory symptoms of PCP like breathlessness, cough, and fever were enrolled. Bronchoalveolar lavage (BAL) samples were collected and homogenized, and then smears were prepared for examination by Gomorimethanamine silver staining (GMSS), Immunofluorescent staining (IFAT), Toludine blue O (TBO), and Giemsa staining. Further, RT-PCR was also performed for the detection of PCP. The mean patients' age was 52 (SD ± 16) years. 41% were female, and 59% of the patients were male. Weight loss (80%), fever (92%), cough (100%), and dyspnea (76%) were the most common complaints. Twenty-eight patients have been diagnosed with pulmonary infiltrates using chest X-ray. Out of 100 patients, 35% were positive for PCP. The organism was detected using IFAT in all the 35 specimens, 15 of 35 (42.86%) by GMSS, 8 of 35 (17.6%) by Giemsa stain, and 1 of 35 (2.8%) was detected by TBO stains. RT-PCR showed that 39 patients was found to be positive for PCP. Thirty-five of these 39 patients had a positive IFAT (89.74%); the IFAT was negative or undefined in 4 samples. All 39 patients (100%) had signs and symptoms for PCP. Our results suggest that RT-PCR is still the most highly sensitive method for detection. In poor resource settings where RT-PCR and IFAT is not available, diagnosis of pneumonia remains a complicated issue. In settings where RT-PCR & IFAT are not available, GMSS staining may be the next best choice to detect PCP.
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http://dx.doi.org/10.1016/j.sjbs.2020.04.032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7254037PMC
June 2020

Computational and in vitro characterization of ICY-5: A potential candidate promoting mitochondrial apoptosis via the c-MET and STAT3 pathways.

J Cell Physiol 2021 Jan 2;236(1):146-156. Epub 2020 Jun 2.

Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia.

Targeted chemotherapy remains the primary choice in controlling various forms of breast cancer (BC) due to its heterogenous gene expressions in various subtypes. In silico and in vitro evaluation of ICY-5, a novel arylidene analogue against c-MET, was performed. ICY-5 exhibited a docking score of -9.6 kcal/mol in inactive conformation and, - 8.6 kcal/mol in active conformation for c-MET. ICY-5 inhibited c-MET enzyme with an IC of 34.34 nM. The compound effectively inhibited MDA-MB 231 and MCF-7 cell proliferation, with GI values of 62.61 and 75.31 nM, respectively, and hepatocyte growth factor (HGF)/R c-MET phosphorylation with IC s of 71.41 and 83.77 nM, respectively. ICY-5 dose-dependently inhibited HGF-induced transmigration, cell scattering, invasion and altered cell cycle. An increase in apoptotic populations of these cells, with a dose-dependent decease in phosphorylation of STAT3 protein was observed. Furthermore, ICY-5 upregulated the caspase-3, caspase-9, Bcl-2-associated X and survivin, and downregulated Bcl-2, vascular endothelial growth factor, matrix metalloproteinase-2 (MMP-2), and MMP-9 in both BC cell lines. In summary, ICY-5 exhibited excellent efficacy in BC cells, targeting c-MET/SAT-3-mediated mitochondrial apoptosis. Further research will be required to ascertain ICY-5 suitability as a targeted chemotherapeutic against multiple forms of BC.
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http://dx.doi.org/10.1002/jcp.29830DOI Listing
January 2021
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