Publications by authors named "Ji-Eun Hong"

28 Publications

  • Page 1 of 1

Photo-Oxidative Protection of Chlorophyll in C-Phycocyanin Aqueous Medium.

Antioxidants (Basel) 2020 Dec 5;9(12). Epub 2020 Dec 5.

Department of Biomedical Engineering, Sogang University, Baekbeom-ro 35, Mapo-gu, Seoul 04107, Korea.

In this study, potential protection of chlorophyll from illumination and oxidation-induced decomposition has been examined using C-phycocyanin (C-PC) aqueous medium. Photo-oxidation resistance of chlorophyll was monitored in various aqueous media using ultraviolet-visible spectroscopy and direct-infusion atmospheric pressure chemical ionization mass spectrometry analysis. The spectroscopy results showed that chlorophyll in C-PC medium experienced the lowest rate of conversion to its derivatives; thus, it was demonstrated that chlorophyll was mostly intact in the C-PC medium. Furthermore, the C-PC treated with chlorophyll showed the lowest concentrations of malondialdehyde, and chlorophyll in C-PC medium did not cause serious damage to human liver cells in vitro after intensive illumination. Therefore, we propose a new method of protecting chlorophyll from photodegradation and oxidation using C-PC aqueous medium.
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http://dx.doi.org/10.3390/antiox9121235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762101PMC
December 2020

Efficacy and safety of So-Cheong-Ryong-Tang in patients with atopic dermatitis and respiratory disorders: Study protocol of a double-blind randomized placebo-controlled trial.

Medicine (Baltimore) 2020 Jan;99(2):e18565

Department of Korean Medicine Ophthalmology and Otolaryngology and Dermatology, Won-Kwang University Korean Medicine Hospital.

Background: Atopic dermatitis (AD, atopic eczema) is a pruritic, inflammatory, chronic skin disease. Since there is limitation of conventional treatment of AD, traditional herbal medicine can be an attractive therapeutic option in patients having AD for a long time. So-Cheong-Ryong-Tang (SCRT) has been found to inhibit histamine release and degranulation of mast cells, differentiation of basophils, and proliferation of eosinophils. We designed this clinical trial to evaluate the efficacy and safety of SCRT as compared to placebo in patients with AD and respiratory disorders.

Methods/design: This study is a single-center, randomized, double-blind, placebo-controlled, and investigator-initiated clinical trial. A total of 60 patients between 7 and 65 years of age with AD and respiratory disorders who received a diagnosis of AD by Hanifin and Rajka criteria who scored 15 to 50 in a scoring atopic dermatitis (SCORAD) will be enrolled. Participants will be randomly assigned to the SCRT or placebo group in a ratio of 1:1 and they will have a visit schedule comprising 4 visits including a screening visit during 8 to 10 weeks. The participants will be administered SCRT or placebo 3 times a day for 4 weeks. The primary outcome will be measured by a change of the SCORAD index. The secondary outcomes will be measured by changes in the dose and frequency of usage of the AD ointment, dermatology life quality index scores, pruritus and sleep disorder in visual analog scale, skin moisture content, skin surface temperature, Hamilton anxiety rating scale scores, depression rating scale scores, stress/autonomic nervous function test, and attention deficit hyperactivity disorder survey scores at week 4 as compared to those at the baseline.

Discussion: To the best of our knowledge, SCRT has rarely been reported for dermatologic diseases. This will be the first clinical trial to assess the efficacy and safety of SCRT in patients with AD and respiratory disorders. We hope that the results of this trial will provide evidence for the use of SCRT as a new treatment for AD with respiratory disorders.

Trial Registration: Korean National Clinical Trial Registry, Clinical Research Information Service. (KCT0004148) (https://cris.nih.go.kr/cris/search/search_result_st01_en.jsp?seq=14981<ype=&rtype=).
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http://dx.doi.org/10.1097/MD.0000000000018565DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6959861PMC
January 2020

Association of atopic dermatitis with obesity via a multi-omics approach: A protocol for a case-control study.

Medicine (Baltimore) 2019 Jul;98(29):e16527

Department of Korean Medicine Ophthalmology and Otolaryngology and Dermatology, Wonkwang University Iksan Korean Medicine Hospital, Iksan, Republic of Korea.

Introduction: Several studies have found that obesity is associated with atopic dermatitis (AD); however, the mechanisms underlying the association are largely unknown. This study aims to assess the association of AD with obesity in the Korean population and verify its mechanism via a multi-omics analysis.

Methods And Analysis: A case-control study will be conducted in the Republic of Korea. A total of 80 subjects, aged 4 to 12 years, matched for age and sex, with body mass index at or above the 85th percentile or at or below the 25th percentile, will be included. Subjects will be assigned to the following 4 groups: obese/overweight with AD, normal/underweight with AD, obese/overweight control, and normal/underweight control. Serum metabolome and immune biomarkers, as well as fecal metabolome and microbiome biomarkers, will be analyzed. Serum eosinophil cationic protein, total serum Immunoglobulin E (IgE), and specific IgE will be analyzed to assess allergic tendency. The SCORing of AD index, the children's dermatology life quality index, body composition analysis, and the Korean gastrointestinal symptom rating scale will be obtained to assess the disease status and severity of the subjects.

Discussion: The findings of this study are expected to provide evidence of an association between AD and obesity via a gut microbiome-metabolome-immune mechanism. Therefore, it may improve future management strategies for AD.

Trial Registration: This study has been registered at the Korean National Clinical Trial Registry, Clinical Research Information Service (KCT0003630).
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http://dx.doi.org/10.1097/MD.0000000000016527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6708792PMC
July 2019

Efficacy and safety of Soshiho-tang in patients with atopic dermatitis and gastrointestinal disorders: Study protocol for a double-blind, randomized, and placebo-controlled clinical trial.

Medicine (Baltimore) 2019 May;98(18):e15479

Department of Korean Medicine Ophthalmology and Otolaryngology and Dermatology, Won-Kwang University Korean Medicine Hospital, Iksan-si, Jeollabuk-do, Republic of Korea.

Background: Atopic dermatitis (AD) is a chronically relapsing inflammatory skin disease that affects the quality of life in patients with AD. Since there is limitation of conventional treatment of AD, complementary treatment is required to treat AD symptoms more effectively and safely Soshiho-tang (SSHT) is a traditional herbal medicine that exhibits anti-inflammatory and anti-ulcer effects and improves the immune function. In this clinical trial, we will evaluate the efficacy and safety of SSHT in patients with AD and gastrointestinal disorders in comparison with placebo.

Methods/design: This study is a single-center, randomized, double-blind, placebo-controlled, and investigator-initiated clinical trial. A total of 60 patients aged 3 to 18 years with AD and gastrointestinal disorders and who received a diagnosis of AD by Hanifin & Rajka criteria with a Scoring Atopic Dermatitis (SCORAD) index between 15 and 49 will be enrolled. Participants will be randomly assigned to the SSHT or placebo group in a ratio of 1:1. Additionally, they will have a visit schedule comprising 4 visits including a screening visit during 8 to 10 weeks. The participants will be administered SSHT or placebo 3 times a day for 4 weeks. The primary outcome will be measured by a change of the SCORAD index. The secondary outcome measures include the following: survey questionnaires for the perception of gastrointestinal disorders, amount and frequency of ointment usage for AD, dermatology quality of life index, itchiness and sleep disability score in visual analog scale, percutaneous water loss, skin surface temperature, Hamilton anxiety rating scale, and children's depression inventory.

Discussion: In our knowledge, this will be the first clinical trial to assess the efficacy and safety of SSHT in patients with AD and gastrointestinal disorders. The findings of this study will provide new treatment options for patients with AD and gastrointestinal disorders.

Trial Registration: Korean National Clinical Trial Registry, Clinical Research Information Service. (KCT0003713) https://cris.nih.go.kr/cris/search/search_result_st01_en.jsp?seq=13489<ype=&rtype=.
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http://dx.doi.org/10.1097/MD.0000000000015479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6504306PMC
May 2019

Alveolar Macrophages Treated With Spore Protect Mice Infected With Respiratory Syncytial Virus A2.

Front Microbiol 2019 12;10:447. Epub 2019 Mar 12.

Department of Agricultural Biotechnology, Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul, South Korea.

Respiratory syncytial virus (RSV) is a major pathogen that infects lower respiratory tract and causes a common respiratory disease. Despite serious pathological consequences with this virus, effective treatments for controlling RSV infection remain unsolved, along with poor innate immune responses induced at the initial stage of RSV infection. Such a poor innate defense mechanism against RSV leads us to study the role of alveolar macrophage (AM) that is one of the primary innate immune cell types in the respiratory tract and may contribute to protective responses against RSV infection. As an effective strategy for enhancing anti-viral function of AM, this study suggests the intranasal administration of spore which induces expansion of AM in the lung with activation and enhanced production of inflammatory cytokines along with several genes associated with M1 macrophage differentiation. Such effect by spore on AM was largely dependent on TLR-MyD88 signaling and, most importantly, resulted in a profound reduction of viral titers and pathological lung injury upon RSV infection. Taken together, our results suggest a protective role of AM in RSV infection and its functional modulation by spore, which may be a useful and potential therapeutic approach against RSV.
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http://dx.doi.org/10.3389/fmicb.2019.00447DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6423497PMC
March 2019

Patient-Derived Xenograft Models of Epithelial Ovarian Cancer for Preclinical Studies.

Cancer Res Treat 2017 Oct 4;49(4):915-926. Epub 2017 Jan 4.

Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Purpose: Patient-derived tumor xenografts (PDXs) can provide more reliable information about tumor biology than cell line models. We developed PDXs for epithelial ovarian cancer (EOC) that have histopathologic and genetic similarities to the primary patient tissues and evaluated their potential for use as a platform for translational EOC research.

Materials And Methods: We successfully established PDXs by subrenal capsule implantation of primary EOC tissues into female BALB/C-nude mice. The rate of successful PDX engraftment was 48.8% (22/45 cases). Hematoxylin and eosin staining and short tandem repeat analysis showed histopathological and genetic similarity between the PDX and primary patient tissues.

Results: Patients whose tumors were successfully engrafted in mice had significantly inferior overall survival when compared with those whose tumors failed to engraft (p=0.040). In preclinical tests of this model, we found that paclitaxel-carboplatin combination chemotherapy significantly deceased tumor weight in PDXs compared with the control treatment (p=0.013). Moreover, erlotinib treatment significantly decreased tumor weight in epidermal growth factor receptor-overexpressing PDX with clear cell histology (p=0.023).

Conclusion: PDXs for EOC with histopathological and genetic stability can be efficiently developed by subrenal capsule implantation and have the potential to provide a promising platform for future translational research and precision medicine for EOC.
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http://dx.doi.org/10.4143/crt.2016.322DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5654149PMC
October 2017

Dynamin 2 Inhibitors as Novel Therapeutic Agents Against Cervical Cancer Cells.

Anticancer Res 2016 12;36(12):6381-6388

Department of Pathology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea

Aim: We investigated the feasibility of dynamin 2 as a potential treatment target in cervical cancer cells.

Materials And Methods: We performed tissue microarray for dynamin 2 expression in 208 patients with early cervical cancer and in vitro in HeLa cells with dynamin 2 inhibitors MiTMAB, OcTMAB, Dynasore, and DD-6.

Results: Tumor size greater than 2 cm or tumor invasion of more than half of the entire cervix was associated with expression of dynamin 2 compared to no expression (p=0.013, and p=0.045, respectively). All dynamin 2 inhibitors significantly reduced proliferation, increased apoptotic activity, and reduced matrix metallopeptidase 9 expression in HeLa cells. Dynasore and DD-6 reduced migration of HeLa cells on laminin 1-coated plates and DD-6 most strongly reduced migration performance on fibronectin-coated plates.

Conclusion: Targeting dynamin 2 may be a promising new approach for the treatment of cervical cancer.
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http://dx.doi.org/10.21873/anticanres.11235DOI Listing
December 2016

Proton Pump Inhibition Enhances the Cytotoxicity of Paclitaxel in Cervical Cancer.

Cancer Res Treat 2017 Jul 27;49(3):595-606. Epub 2016 Sep 27.

Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Purpose: This study was conducted to investigate whether a proton pump inhibitor (PPI) could enhance chemosensitivity via the inhibition of vacuolar-type H ATPase (V-ATPase) in cervical cancer.

Materials And Methods: The expression of V-ATPase was evaluated in 351 formalin-fixed, paraffin-embedded human cervical cancer tissues using immunohistochemistry and compared with clinicopathologic risk factors for disease prognosis. The influence of cell proliferation and apoptosis following V-ATPase siRNA transfection or esomeprazole pretreatment was assessed in cervical cancer cell lines using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and enzyme-linked immunosorbent assay, respectively.

Results: Immunohistochemical analysis revealed that V-ATPase was expressed in about 60% of cervical cancer tissue samples (211/351), and the expression was predominantly found in adenocarcinoma histology (p=0.016). Among patients with initially bulky cervical cancer (n=89), those with V-ATPase expression had shorter disease-free survival (p=0.005) and overall survival (p=0.023). Co-treatment with V-ATPase siRNA or esomeprazole with paclitaxel significantly decreased the cell proliferation of cervical cancer cell lines, including HeLa and INT407, compared to cell lines treated with paclitaxel alone (p < 0.01). Moreover, V-ATPase siRNA or esomeprazole followed by paclitaxel significantly increased the expression of active caspase-3 in these cells compared to cells treated with paclitaxel alone (both, p < 0.05).

Conclusion: V-ATPase was predominantly expressed in cervical adenocarcinoma, and the expression of V-ATPases was associated with poor prognosis. The inhibition of V-ATPase via siRNA or PPI (esomeprazole) might enhance the chemosensitivity of paclitaxel in cervical cancer cells.
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http://dx.doi.org/10.4143/crt.2016.034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5512380PMC
July 2017

Synergistic inhibitory effect of cetuximab and tectochrysin on human colon cancer cell growth via inhibition of EGFR signal.

Arch Pharm Res 2016 May 29;39(5):721-9. Epub 2016 Mar 29.

College of Pharmacy and Medical Research Center, Chungbuk National University, 194-31 Osongsaengmyeong 1-ro, Osong-eup, Heungdeok-gu, Cheongju, Chungbuk, 361-951, Republic of Korea.

The purpose of this study was to evaluate the enhancing potency of tectochrysin, a flavonoid isolated from Alpinia oxyphylla Miquel by combining cetuximab, an anti-EGFR monoclonal antibody, on human colon cancer cell growth through further inhibition of EGFR pathway. HCT116 and SW480 colon cancer cells were treated with cetuximab (30 μg/mL, 1/10 of IC50), tectochrysin (5 μg/mL, 1/3 of IC50), or the combination of both agents. The growth inhibitory effect was examined using the MTT assay while apoptotic cell death was performed using TUNEL staining assays. The DNA binding activity of NF-kappa B and AP-1 was investigated by electrophoretic mobility shift assay. Protein expression was determined by Western blot. Cell proliferation was significantly inhibited by the combination of cetuximab and tectochrysin than treatment with cetuximab or tectochrysin alone (combination index: 0.572 and 0.533, respectively). Combination treatment of cells with cetuximab and tectochrysin significantly reduced the expressions of p-EGFR and COX-2 in both cell lines. Combination treatment also significantly inhibited activities of NF-kB and AP-1 compared to the single agent treatment. Our results indicate that combined therapy with lower concentration of cetuximab and tectochrysin could significantly enhance the cancer cell growth inhibitory effect through the inhibition of EGFR signaling.
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http://dx.doi.org/10.1007/s12272-016-0735-7DOI Listing
May 2016

Synergistic Inhibitory Effects of Cetuximab and Cisplatin on Human Colon Cancer Cell Growth via Inhibition of the ERK-Dependent EGF Receptor Signaling Pathway.

Biomed Res Int 2015 28;2015:397563. Epub 2015 Sep 28.

College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju, Chungbuk 361-763, Republic of Korea.

The purpose of this study was to evaluate the anticancer efficacy of cetuximab combined with cisplatin (combination treatment) on colon cancer growth, as well as its underlying action mechanism. Combination treatment synergistically potentiated the effect of cetuximab on cell growth inhibition and apoptosis induction in HCT116 and SW480 cells. Combination treatment further suppressed the expression of the activated form of epidermal growth factor receptor (EGFR) and MAP kinase (p-ERK and p-p38) and also significantly inhibited the activity of activator protein-1 (AP-1) and nuclear factor kappa B (NF-κB). Additionally, the expression of cyclooxygenase-2 (COX-2) and interleukin-8 (IL-8) mRNA was significantly reduced by the combination treatment as compared to the expression seen for treatment with cetuximab or cisplatin alone. We found that the synergistic inhibitory effects of cetuximab and cisplatin on AP-1 and NF-κB activation, as well as on cell viability, were reversed by pretreatment with an ERK inhibitor. Results demonstrate that combined treatment with cetuximab and cisplatin exerts synergistic anticancer effects on colon cancer cells and also suggest that the ERK pathway plays a critical role in these effects via the suppression of the EGFR signaling pathway, along with the inhibition of COX-2, IL-8, and AP-1 and NF-κB.
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http://dx.doi.org/10.1155/2015/397563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4600871PMC
August 2016

Proton pump inhibitors enhance the effects of cytotoxic agents in chemoresistant epithelial ovarian carcinoma.

Oncotarget 2015 Oct;6(33):35040-50

Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

This study was designed to investigate whether proton pump inhibitors (PPI, V-ATPase blocker) could increase the effect of cytotoxic agents in chemoresistant epithelial ovarian cancer (EOC). Expression of V-ATPase protein was evaluated in patients with EOC using immunohistochemistry, and patient survival was compared based on expression of V-ATPase mRNA from a TCGA data set. In vitro, EOC cell lines were treated with chemotherapeutic agents with or without V-ATPase siRNA or PPI (omeprazole) pretreatment. Cell survival and apoptosis was assessed using MTT assay and ELISA, respectively. In vivo experiments were performed to confirm the synergistic effect with omeprazole and paclitaxel on tumor growth in orthotopic and patient-derived xenograft (PDX) mouse models. Expression of V-ATPase protein in ovarian cancer tissues was observed in 44 patients (44/59, 74.6%). Higher expression of V-ATPase mRNA was associated with poorer overall survival in TCGA data. Inhibition of V-ATPase by siRNA or omeprazole significantly increased cytotoxicity or apoptosis to paclitaxel in chemoresistant (HeyA8-MDR, SKOV3-TR) and clear cell carcinoma cells (ES-2, RMG-1), but not in chemosensitive cells (HeyA8, SKOV3ip1). Moreover, the combination of omeprazole and paclitaxel significantly decreased the total tumor weight compared with paclitaxel alone in a chemoresistant EOC animal model and a PDX model of clear cell carcinoma. However, this finding was not observed in chemosensitive EOC animal models. These results show that omeprazole pretreatment can increase the effect of chemotherapeutic agents in chemoresistant EOC and clear cell carcinoma via reduction of the acidic tumor microenvironment.
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http://dx.doi.org/10.18632/oncotarget.5319DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4741507PMC
October 2015

Anticancer effect of tectochrysin in colon cancer cell via suppression of NF-kappaB activity and enhancement of death receptor expression.

Mol Cancer 2015 Jun 30;14:124. Epub 2015 Jun 30.

College of Pharmacy and Medical Research Center, Chungbuk National University, 194-31 Osongsaengmyeong 1-ro, Osong-eup, Heungdeok-gu, Cheongju, Chungbuk, 361-951, Republic of Korea.

Background: Flavonoids are a diverse family of natural phenolic compounds commonly found in fruits and vegetables. Epidemiologic studies showed that flavonoids also reduce the risk of colon cancer. Tectochrysin is one of the major flavonoids of Alpinia oxyphylla Miquel. However, the anti-cancer effects and the molecular mechanisms of tectochrysin in colon cancer cells have not yet been reported. We investigated whether tectochrysin could inhibit colon cancer cell growth at 1, 5, 10 μg/ml. In in vivo study, we injected a tectochrysin treatment dose of 5 mg/kg to each mouse.

Results: Tectochrysin suppressed the growth of SW480 and HCT116 human colon cancer cells. The expression of DR3, DR4 and Fas were significantly increased, and pro-apoptotic proteins were also increased. Tectochrysin treatment also inhibited activity of NF-κB. A docking model indicated that tectochrysin binds directly to the p50 unit. In in vivo, tumor weights and volumes in mice were reduced when treated with tectochrysin. Tectochrysin leads to apoptotic cell death in colon cancer cells through activation of death receptors expression via the inhibition of NF-κB.

Conclusions: Tectochrysin can be a useful agent for the treatment of colon cancer cell growth as well as an adjuvant agent for chemo-resistant cancer cells growth.
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http://dx.doi.org/10.1186/s12943-015-0377-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4487202PMC
June 2015

Effect of grain size on thermal transport in post-annealed antimony telluride thin films.

Nanoscale Res Lett 2015 28;10:20. Epub 2015 Jan 28.

Department of Physics, Chung-Ang University, Seoul, 156-756 Republic of Korea.

The effects of grain size and strain on the temperature-dependent thermal transport of antimony telluride (Sb2Te3) thin films, controlled using post-annealing temperatures of 200°C to 350°C, were investigated using the 3-omega method. The measured total thermal conductivities of 400-nm-thick thin films annealed at temperatures of 200°C, 250°C, 300°C, 320°C, and 350°C were determined to be 2.0 to 3.7 W/m · K in the 20 to 300 K temperature range. We found that the film grain size, rather than the strain, had the most prominent effect on the reduction of the total thermal conductivity. To confirm the effect of grain size on temperature-dependent thermal transport in the thin films, the experimental results were analyzed using a modified Callaway model approach.
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http://dx.doi.org/10.1186/s11671-015-0733-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4384892PMC
April 2015

Interleukin-32β ameliorates metabolic disorder and liver damage in mice fed high-fat diet.

Obesity (Silver Spring) 2015 Mar 3;23(3):615-22. Epub 2015 Feb 3.

College of Pharmacy, Chungbuk National University, Heungduk-gu, Cheongju, Chungbuk, Republic of Korea.

Objective: Chronic excessive food intake leads to energy imbalance, resulting in hepatic steatosis and inflammation. Interleukin-32 (IL-32) is known to be a pro-inflammatory cytokine associated with chronic inflammation and cancer. Therefore, the relationship between IL-32 and chronic excessive food intake-induced liver disease was investigated.

Methods: Male IL-32β transgenic and wild-type mice were fed a high-fat diet (HFD) for 15 weeks. They were compared with wild-type mice on a standard chow diet. Daily food intake, body and liver weight, serum biochemistry, histopathological analysis of the liver, and hepatic immune response were determined.

Results: IL-32β mice on HFD showed lower lipid accumulation, reduced infiltration of immune cells, and lower production of pro-inflammatory cytokines in the liver. The expression of the peroxisome proliferator-activated receptor γ (PPARγ) was downregulated and the adenosine 50-monophosphate (AMP)-activated protein kinase (AMPK) was activated in the liver of IL-32β mice compared to wild-type mice. Furthermore, IL-32β over-expression activated the AMPK pathway and IL-32β downregulation inactivated the AMPK pathway in HepG2 cells under high-glucose conditions.

Conclusions: These data suggest that IL-32β modulates lipid accumulation through inhibition of PPARγ expression and AMPK activation.
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http://dx.doi.org/10.1002/oby.21001DOI Listing
March 2015

Inhibitory effect of snake venom toxin on NF-κB activity prevents human cervical cancer cell growth via increase of death receptor 3 and 5 expression.

Arch Toxicol 2016 Feb 23;90(2):463-77. Epub 2014 Nov 23.

College of Pharmacy and Medical Research Center, Chungbuk National University, 12 Gaeshin-dong, Heungduk-gu, Cheongju, Chungbuk, 316-200, Republic of Korea.

We previously found that snake venom toxin inhibits nuclear factor kappa B (NF-κB) activity in several cancer cells. NF-κB is implicated in cancer cell growth and chemoresistance. In our present study, we investigated whether snake venom toxin (SVT) inhibits NF-κB, thereby preventing human cervical cancer cell growth (Ca Ski and C33A). SVT (0-12 μg/ml) inhibited the growth of cervical cancer cells by the induction of apoptotic cell death. These inhibitory effects were associated with the inhibition of NF-κB activity. However, SVT dose dependently increased the expression of death receptors (DRs): DR3, DR5 and DR downstream pro-apoptotic proteins. Exploration of NF-κB inhibitor (Phenylarsine oxide, 0.1 μM) synergistically further increased SVT-induced DR3 and DR5 expressions accompanied with further inhibition of cancer cells growth. Moreover, deletion of DR3 and DR5 by small interfering RNA significantly abolished SVT-induced cell growth inhibitory effects, as well as NF-κB inactivation. Using TNF-related apoptosis-inducing ligand resistance cancer cells (A549 and MCF-7), we also found that SVT enhanced the susceptibility of chemoresistance of these cancer cells through down-regulation of NF-κB, but up-regulation of DR3 and DR5. In vivo study also showed that SVT (0.5 and 1 mg/kg) inhibited tumor growth accompanied with inactivation of NF-κB. Thus, our present study indicates that SVT could be applicable as an anticancer agent for cervical cancer, or as an adjuvant agent for chemoresistant cancer cells.
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http://dx.doi.org/10.1007/s00204-014-1393-5DOI Listing
February 2016

Neuroinflammatory and Amyloidogenic Activities of IL-32β in Alzheimer's Disease.

Mol Neurobiol 2015 Aug 27;52(1):341-52. Epub 2014 Aug 27.

College of Pharmacy, Medical Research Center, Chungbuk National University, 12 Gaesin-dong, Heungduk-gu, Cheongju, Chungbuk, 361-763, South Korea.

Interleukin (IL)-32β can act as either pro-inflammatory or anti-inflammatory cytokines with being dependent on the status of disease development. Herein, we investigated whether IL-32β overexpression changes cytokine levels and affects amyloid-beta (Aβ)-induced pro-inflammation in the brain. IL-32β transgenic (Tg) mice and non-Tg mice were intracerebroventricularly infused with Aβ1-42 once a day for 14 days, and then cognitive function was assessed by the Morris water maze test and passive avoidance test. Our data showed that IL-32β Tg mice increased memory impairment, glia activation, amyloidogenesis, and neuroinflammation. The expression of glial fibrillary acid protein (GFAP), Iba1, and β-secretase 1 (BACE1) in the cortex and hippocampus was much higher in the Aβ1-42-infused IL-32β Tg mice brain. The activation of signal transducer and activator of transcription 3 (STAT3) and nuclear factor-kappa B (NF-κB) was much higher in Aβ1-42-infused IL-32β Tg mice brain. We also found that cytokines including IP-10, GM-CSF, JE, IL-13, and interferone-inducible T cell α chemoattractant (I-TAC) were elevated in Aβ1-42-infused IL-32β Tg mice brain. These results suggest that IL-32β could activate NF-κB and STAT3, and thus affect neuroinflammation as well as amyloidogenesis, leading to worsening memory impairment.
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http://dx.doi.org/10.1007/s12035-014-8860-0DOI Listing
August 2015

Rubus coreanus Miquel ameliorates scopolamine-induced memory impairments in ICR mice.

J Med Food 2014 Oct 14;17(10):1049-56. Epub 2014 Aug 14.

1 Center for Efficacy Assessment and Development of Functional Foods and Drugs, Hallym University , Chuncheon, Korea.

The present study investigated the effect of Rubus coreanus Miquel (RCM) on scopolamine-induced memory impairments in ICR mice. Mice were orally administrated RCM for 4 weeks and scopolamine was intraperitoneally injected into mice to induce memory impairment. RCM improved the scopolamine-induced memory impairment in mice. The increase of acetylcholinesterase activity caused by scopolamine was significantly attenuated by RCM treatment. RCM increased the levels of acetylcholine in the brain and serum of mice. The expression of choline acetyltransferase, phospho-cyclic AMP response element-binding protein, and phospho-extracellular signal-regulated kinase was significantly increased within the brain of mice treated with RCM. The brain antioxidant enzyme activity decreased by scopolamine was increased by RCM. These results demonstrate that RCM exerts a memory-enhancing effect via the improvement of cholinergic function and the potentiated antioxidant activity in memory-impaired mice. The results suggest that RCM may be a useful agent for improving memory impairment.
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http://dx.doi.org/10.1089/jmf.2013.3004DOI Listing
October 2014

Escin suppresses migration and invasion involving the alteration of CXCL16/CXCR6 axis in human gastric adenocarcinoma AGS cells.

Nutr Cancer 2014 9;66(6):938-45. Epub 2014 Jun 9.

a Department of Food Science & Nutrition , Dongseo University , Busan , Korea.

Escin, a natural mixture of triterpene saponins isolated from horse chestnut, has been reported to possess anticancer activity in many human cancer cells. However, the effect of escin on the metastasis has not been studied. The present study examined the effect of escin on the migration and invasion of AGS human gastric cancer cells. To examine the effects of escin on metastatic capacities of gastric cancer cells, AGS cells were cultured in the presence of 0-4 μmol/L escin. Escin inhibited cell migration and invasion in AGS cells. However, escin did not affect the viability of these cells at these concentrations. The chemokine receptor and its ligands play an important role in cancer metastasis. Escin decreased the production of soluble C-X-C motif chemokine (CXCL)16 but increased the expression of trans-membranous CXCL16. The expression of C-X-C chemokine receptor (CXCR)6 was not affected by escin treatment. Exogenous CXCL16 reversed escin-induced migration inhibition. In addition, escin inhibited the phosphorylation of focal adhesion kinase and Akt. These results demonstrate that escin inhibited the migration and invasion of AGS cells, which is associated with altered CXCL16/CXCR6 axis. These findings suggest that escin has potential as an antimetastatic agent in gastric cancer.
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http://dx.doi.org/10.1080/01635581.2014.922202DOI Listing
April 2015

Functional characteristics of porcine peripheral T cells stimulated with IL-2 or IL-2 and PMA.

Res Vet Sci 2014 Feb 10;96(1):54-61. Epub 2013 Dec 10.

Department of Agricultural Biotechnology, and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea; Center for Food and Bioconvergence, Seoul National University, Seoul, Republic of Korea. Electronic address:

In human or mouse, mature T cells express either CD4 or CD8, resulting in different functions in the periphery. Interestingly, porcine CD4 and CD8 double positive (DP) T cells are present in the blood, and their proportions change from youth to adulthood. However, the features of these cells in swine are poorly understood. We investigated the fate of porcine peripheral T cells based on their functional characteristics, including proliferation and the expression of CD4 and CD8 co-receptors. The results showed that all the populations changed their CD8 expression in a time-dependent manner and porcine T cells had different proliferative pattern from human T cells. The results further revealed that Th2 cytokines were increased later in porcine T cells compared to human T cells upon stimulation with IL-2+PMA. Collectively, we found that the fate of porcine peripheral T cells is different from that of human T cells, and the changes occur in a time- and stimulation-dependent manner.
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http://dx.doi.org/10.1016/j.rvsc.2013.11.018DOI Listing
February 2014

Biological features of core networks that result from a high-fat diet in hepatic and pulmonary tissues in mammary tumour-bearing, obesity-resistant mice.

Br J Nutr 2013 Jul 13;110(2):241-55. Epub 2012 Dec 13.

Center for Efficacy Assessment and Development of Functional Foods and Drugs, Hallym University, 1 Hallymdaehak-gil, Chuncheon 200-702, Republic of Korea.

We previously demonstrated that the chronic consumption of a high-fat diet (HFD) promotes lung and liver metastases of 4T1 mammary carcinoma cells in obesity-resistant BALB/c mice. To examine early transcriptional responses to tumour progression in the liver and lungs of HFD-fed mice, 4-week-old female BALB/c mice were divided into four groups: sham-injected, control diet (CD)-fed; sham-injected, HFD-fed (SH); 4T1 cell-injected, CD-fed (TC); 4T1 cell-injected, HFD-fed (TH). Following 16 weeks of either a CD or HFD, 4T1 cells were injected into the mammary fat pads of mice in the TC and TH groups and all mice were continuously fed identical diets. At 14 d post-injection, RNA was isolated from hepatic and pulmonary tissues for microarray analysis of mRNA expression. Functional annotation and core network analyses were conducted for the TH/SH Unique gene set. Inflammation in hepatic tissues and cell mitosis in pulmonary tissues were the most significant biological functions in the TH/SH Unique gene set. The biological core networks of the hepatic TH/SH Unique gene set were characterised as those genes involved in the activation of acute inflammatory responses (Orm1, Lbp, Hp and Cfb), disordered lipid metabolism and deregulated cell cycle progression. Networks of the pulmonary Unique gene set displayed the deregulation of cell cycle progression (Cdc20, Cdk1 and Bub1b). These HFD-influenced alterations may have led to favourable conditions for the formation of both pro-inflammatory and pro-mitotic microenvironments in the target organs that promote immune cell infiltration and differentiation, as well as the infiltration and proliferation of metastatic tumour cells.
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http://dx.doi.org/10.1017/S0007114512004965DOI Listing
July 2013

Mutations in the RNA exosome component gene EXOSC3 cause pontocerebellar hypoplasia and spinal motor neuron degeneration.

Nat Genet 2012 Apr 29;44(6):704-8. Epub 2012 Apr 29.

Department of Neurology, University of California, Los Angeles, California, USA.

RNA exosomes are multi-subunit complexes conserved throughout evolution and are emerging as the major cellular machinery for processing, surveillance and turnover of a diverse spectrum of coding and noncoding RNA substrates essential for viability. By exome sequencing, we discovered recessive mutations in EXOSC3 (encoding exosome component 3) in four siblings with infantile spinal motor neuron disease, cerebellar atrophy, progressive microcephaly and profound global developmental delay, consistent with pontocerebellar hypoplasia type 1 (PCH1; MIM 607596). We identified mutations in EXOSC3 in an additional 8 of 12 families with PCH1. Morpholino knockdown of exosc3 in zebrafish embryos caused embryonic maldevelopment, resulting in small brain size and poor motility, reminiscent of human clinical features, and these defects were largely rescued by co-injection with wild-type but not mutant exosc3 mRNA. These findings represent the first example of an RNA exosome core component gene that is responsible for a human disease and further implicate dysregulation of RNA processing in cerebellar and spinal motor neuron maldevelopment and degeneration.
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http://dx.doi.org/10.1038/ng.2254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3366034PMC
April 2012

BAI, a 3-aminoindazole derivative, inhibits interleukin-1β-induced expression of cyclooxygenase-2 in A549 human airway cells.

Int J Mol Med 2012 Mar 15;29(3):454-60. Epub 2011 Dec 15.

Department of Medical Genetic Engineering, Keimyung University, Dalseo-gu, Daegu 704-701, Republic of Korea.

Cyclooxygenase (COX)-2 and its products, including PGE2, are key inflammatory mediators. In this study, we have assessed the pharmacological characteristics of BAI, a 3-aminoindazole derivative and a novel cyclin-dependent kinase (CDK) inhibitor, for regulation of COX-2 expression induced by interleukin (IL)-1β in A549 human airway cells. Treatment with BAI strongly inhibited IL-1β-induced expression of COX-2 at both the protein and mRNA levels. Results of luciferase experiments also revealed that BAI treatment reduced IL-1β-induced COX-2 promoter activity. Distinctly, treatment with BAI did not affect IL-1β-induced phospho-rylation of extracellular signal-regulated protein kinase-1/2 (ERK-1/2), p38 mitogen-activated protein kinase (MAPK), and c-Jun N-terminal protein kinase-1/2 (JNK-1/2) and proteolysis of IκB-α, an inhibitor of nuclear factor (NF)-κB, but inhibited IL-1β-induced phosphorylation of histone H1, a target for phosphorylation by CDKs. siRNA transfection experiments demonstrated that knockdown of CDK2 and CDK4 led to a slight reduction of IL-1β-induced histone H1 phosphorylation but had no effect on IL-1β-induced COX-2 expression. Interestingly, additional cell culture experiments showed the ability of BAI to repress the PMA-induced COX-2 expression in A549 cells and serum-dependent COX-2 expression in NCI-H292 cells, a human laryngeal cell line. Collectively, these results demonstrate firstly that BAI downregulates IL-1β-induced COX-2 expression through transcriptional repression, which appears to be independent of CDK2, CDK4, MAPKs and NF-κB, in A549 cells. It is suggested that BAI may be a potential candidate for treatment of the airway inflammatory diseases where COX-2 overexpression is problematic.
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http://dx.doi.org/10.3892/ijmm.2011.863DOI Listing
March 2012

The hexane extract of Saussurea lappa and its active principle, dehydrocostus lactone, inhibit prostate cancer cell migration.

J Med Food 2012 Jan 14;15(1):24-32. Epub 2011 Nov 14.

Center for Efficacy Assessment and Development of Functional Foods and Drugs, Hallym University, Chuncheon, Korea.

Saussurea lappa has been used in Chinese traditional medicine for the treatment of abdominal pain, tenesmus, nausea, and cancer; previous studies have shown that S. lappa also induces G(2) growth arrest and apoptosis in gastric cancer cells. In this study, we investigated the effects of hexane extracts of S. lappa (HESLs) on the migration of DU145 and TRAMP-C2 prostate cancer cells. DU145 and TRAMP-C2 cells were cultured in the presence of 0-4 μg/mL HESL with or without 10 ng/mL epidermal growth factor (EGF). HESL inhibited the basal and EGF-induced migration of prostate cancer cells in a dose-dependent manner, whereas HESL did not influence the viability of these cancer cells under the conditions used in this study. Active fractions of HESL were separated via column chromatography, and the structure of the active principle was determined using (1)H and (13)C nuclear magnetic resonance spectroscopy. The active compound, dehydrocostus lactone (DHCL), in fraction 7 dose-dependently inhibited the basal and EGF-induced migration of prostate cancer cells. HESL and DHCL reduced matrix metalloproteinase (MMP)-9 and tissue inhibitor of metalloproteinase (TIMP)-1 secretion but increased TIMP-2 levels in both the absence and presence of EGF. Our results demonstrate that the inhibition of MMP-9 secretion and the stimulation of TIMP-2 secretion contribute to reduced migration of DU145 cells treated with HESL and DHCL. These results indicate that HESL containing its active principle, DHCL, has potential as an antimetastatic agent for the treatment of prostate cancer.
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http://dx.doi.org/10.1089/jmf.2011.1735DOI Listing
January 2012

Benzyl isothiocyanate inhibits basal and hepatocyte growth factor-stimulated migration of breast cancer cells.

Mol Cell Biochem 2012 Jan 3;359(1-2):431-40. Epub 2011 Sep 3.

Center for Efficacy Assessment and Development of Functional Foods and Drugs, Department of Biochemistry, College of Medicine, Hallym University, 39 Hallymdaehak-gil, Chuncheon, 200-702, Korea.

Benzyl isothiocyanate (BITC), which is found in cruciferous vegetables, has been shown to have anti-carcinogenic properties. Hepatocyte growth factor (HGF) has the ability to stimulate dissociation, migration, and invasion in various tumor cells, and abnormally increased expressions of HGF and its transmembrane tyrosine kinase receptor, c-Met, have previously been detected in human breast cancer, and are associated with high tumor grade and poor prognosis. In this study, in order to assess the mechanisms relevant to the BITC-induced regulation of breast cancer cell migration and invasion, MDA-MB-231 human breast cancer cells and 4T1 murine mammary carcinoma cells were cultured in the presence of 0-4 μmol/l BITC with or without 10 μg/l of HGF. BITC inhibited both the basal and HGF-induced migration of MDA-MB-231 and 4T1 cells in a dose-dependent manner. In MDA-MB-231 cells, BITC reduced both basal and HGF-induced secretion and activity of urokinase-type plasminogen activator (uPA). In addition, BITC increased the protein levels of plasminogen activator inhibitor-1. HGF stimulated c-Met and Akt phosphorylation, but did not affect the phosphorylation of extracellular signal-regulated kinase-1/2 or stress-activated protein/c-jun N-terminal kinase. BITC suppressed NF-κB activity and reduced the HGF-induced phosphorylation of c-Met and Akt in a dose-dependent manner. LY294002, a specific Akt inhibitor, reduced both basal and HGF-induced uPA secretion and migration of MDA-MB-231 cells. In this study, we demonstrated that BITC profoundly inhibits the migration and invasion of MDA-MB-231 cells, which is associated with reduced uPA activity, and also that these phenomena are accompanied by the suppression of Akt signaling.
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http://dx.doi.org/10.1007/s11010-011-1039-3DOI Listing
January 2012

Dietary fat increases solid tumor growth and metastasis of 4T1 murine mammary carcinoma cells and mortality in obesity-resistant BALB/c mice.

Breast Cancer Res 2011 Aug 11;13(4):R78. Epub 2011 Aug 11.

Center for Efficacy Assessment and Development of Functional Foods and Drugs, Hallym University, 39 Hallymdaehak-gil, Chuncheon, 200-702, Korea.

Introduction: High-fat diets (HFDs) are known to cause obesity and are associated with breast cancer progression and metastasis. Because obesity is associated with breast cancer progression, it is important to determine whether dietary fat per se stimulates breast cancer progression in the absence of obesity. This study investigated whether an HFD increases breast cancer growth and metastasis, as well as mortality, in obesity-resistant BALB/c mice.

Methods: The 4-week-old, female BALB/c mice were fed HFD (60% kcal fat) or control diet (CD, 10% kcal fat) for 16 weeks. Subsequently, 4T1 mammary carcinoma cells were injected into the inguinal mammary fat pads of mice fed continuously on their respective diets. Cell-cycle progression, angiogenesis, and immune cells in tumor tissues, proteases and adhesion molecules in the lungs, and serum cytokine levels were analyzed with immunohistochemistry, Western blotting, and enzyme-linked immunosorbent assay (ELISA). In vitro studies were also conducted to evaluate the effects of cytokines on 4T1 cell viability, migration, and adhesion.

Results: Spleen and gonadal fat-pad weights, tumor weight, the number and volume of tumor nodules in the lung and liver, and tumor-associated mortality were increased in the HFD group, with only slight increases in energy intake and body weight. HF feeding increased macrophage infiltration into adipose tissues, the number of lipid vacuoles and the expression of cyclin-dependent kinase (CDK)2, cyclin D1, cyclin A, Ki67, CD31, CD45, and CD68 in the tumor tissues, and elevated serum levels of complement fragment 5a (C5a), interleukin (IL)-16, macrophage colony-stimulating factor (M-CSF), soluble intercellular adhesion molecule (sICAM)-1, tissue inhibitors of metalloproteinase (TIMP)-1, leptin, and triggering receptor expressed on myeloid cells (TREM)-1. Protein levels of the urokinase-type plasminogen activator, ICAM-1, and vascular cell adhesion molecule-1 were increased, but plasminogen activator inhibitor-1 levels were decreased in the lungs of the HFD group. In vitro assays using 4T1 cells showed that sICAM-1 increased viability; TREM-1, TIMP-1, M-CSF, and sICAM-1 increased migration; and C5a, sICAM-1, IL-16, M-CSF, TIMP-1, and TREM-1 increased adhesion.

Conclusions: Dietary fat increases mammary tumor growth and metastasis, thereby increasing mortality in obesity-resistant mice.
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http://dx.doi.org/10.1186/bcr2927DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3236342PMC
August 2011

Oral administration of benzyl-isothiocyanate inhibits solid tumor growth and lung metastasis of 4T1 murine mammary carcinoma cells in BALB/c mice.

Breast Cancer Res Treat 2011 Nov 18;130(1):61-71. Epub 2010 Dec 18.

Center for Efficacy Assessment and Development of Functional Foods and Drugs, Hallym University, Chuncheon, Korea.

Benzyl-isothiocyanate (BITC) is a hydrolysis product of glucotropaeolin, a compound found in cruciferous vegetables, and has also been shown to have anti-tumor properties. To evaluate the effects of BITC administration on the tumor growth and metastasis of breast cancer, 4T1 murine mammary carcinoma cells were injected into the inguinal mammary fat pads of syngeneic female BALB/c mice. One day later, the mice were subjected to gavage for 4 weeks with BITC (0, 5, or 10 mg/kg body weight/day). Oral BITC treatment induced a significant reduction in the growth of solid tumors. BITC reduced hemoglobin contents and CD31 and vascular endothelial growth factor (VEGF) expression in the tumors, as well as circulating levels of VEGF. Reduced expressions of proliferating cell nuclear antigen and cyclin-dependent kinase 4 were noted in the tumors of BITC-treated mice. BITC markedly increased the numbers of apoptotic cells with increased Bax expression, cleaved caspase-3, and PARP levels, but reduced Bcl-2 expression in tumor tissues. In addition, BITC was shown to reduce the numbers of pulmonary tumor nodules and the total pulmonary metastatic volume. BITC induced a significant reduction in the levels of matrix metalloproteinase (MMP)-2, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1, and urokinase-type plasminogen activator in the sera and lungs of 4T1 cell-injected mice. However, the concentrations of TIMP-2 and plasminogen activator inhibitor-1 were increased in the sera and lungs of BITC-treated mice. The results of this study indicate that BITC has potential as a preventive agent for metastatic breast cancer.
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http://dx.doi.org/10.1007/s10549-010-1299-8DOI Listing
November 2011

Oral administration of 3,3'-diindolylmethane inhibits lung metastasis of 4T1 murine mammary carcinoma cells in BALB/c mice.

J Nutr 2009 Dec 28;139(12):2373-9. Epub 2009 Oct 28.

Center for Efficacy Assessment and Development of Functional Foods and Drugs, Hallym University, Chuncheon, Korea.

3,3'-diindolylmethane (DIM) is the major in vivo product of the acid-catalyzed oligomerization of indole-3-carbinol present in cruciferous vegetables, and it has been shown to exhibit anticancer properties. In this study, we assessed the effects of DIM on the metastasis of 4T1 mouse mammary carcinoma cells. In vitro culture studies showed that DIM dose-dependently inhibited the migration, invasion, and adhesion of 4T1 cells at concentrations of 0-10 micromol/L without attendant changes in cell viability. In an in vivo lung metastasis model, 4T1 cells (2 x 10(5) cells/mouse) were injected into the tail veins of syngeneic female BALB/c mice. Beginning on the second day, the mice were subjected to gavage with 0-10 mg DIM/(kg body weight x d) for 13 d. Oral DIM administration resulted in a marked reduction in the number of pulmonary tumor nodules. DIM treatment significantly reduced the levels of matrix metalloproteinase (MMP)-2, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1, and vascular cell adhesion molecule (VCAM)-1 and increased TIMP-2 levels in the sera and lungs of mice injected with 4T1 cells. Additionally, DIM treatment reduced the serum concentrations of interleukin (IL)-1beta, IL-6 and tumor necrosis factor (TNF)alpha. We have demonstrated that DIM profoundly inhibits the lung metastasis of 4T1 cells, which was accompanied by reduced levels of MMP, adhesion molecules, and proinflammatory cytokines. These results indicate that DIM has potential as an antimetastatic agent for the treatment of breast cancer.
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http://dx.doi.org/10.3945/jn.109.111864DOI Listing
December 2009

Synthesis and biological evaluation of 2,5-diaminobenzamide derivatives as anti-proliferating agents.

Arch Pharm Res 2009 Jun 26;32(6):803-12. Epub 2009 Jun 26.

Department of Chemistry, Keimyung University, Daegu 704-701, Korea.

The screening of the chemical library for the anti-proliferative activity of the chemical library provided 2,5-diaminobenzamide as the initial hit. The confirmation and the optimization of hit were performed by synthesis followed by the evaluation of growth inhibitory activity against human cancer cell lines. The most active growth inhibitor showed IC(50) of 1.0 microM. The compound 7 increased not only sub-G1 population but also number of cells which are stained with Annexin V-FITC and 7-AAD, suggesting that compound 7 induced cell death is apoptosis.
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http://dx.doi.org/10.1007/s12272-009-1600-8DOI Listing
June 2009