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RISS 인기검색어
- 검색키워드
- 저자 : Sabarish Ramachandran (검색결과 5 건)
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Sabarish Ramachandran,권건영,신소진,권상훈,차순도,배인수,조치흠 대한의학회 2008 Journal of Korean medical science Vol.23 No.4
The molecular mechanism of the cell-cycle machinery in uterine leiomyoma has not yet been fully elucidated. Among the various types of cell-cycle regulators, p27Kip1 (p27) is considered to be a potent tumor suppressor. To provide further molecular basis for understanding the progression of uterine leiomyoma, our objective was to evaluate the expression level of p27 in normal myometrium and uterine leiomyoma tissue and its effect on cytogenic growth. Western blot analysis, real-time polymerase chain reaction (PCR) and immunohistochemical staining revealed that p27 protein and messenger RNA were down-regulated in uterine leiomyoma tissue and cultured cells compared to normal myometerium. Full-length human p27 cDNA was transferred using a replication-deficient recombinant adenoviral vector (Ad.p27) into uterine leiomyoma cells and evaluated the effect on cell proliferation. Transfection of Ad.p27 into uterine leiomyoma cells resulted in the induction of apoptosis, reduction in viability and proliferation of uterine leiomyoma cells. Our results suggest a new paradigm that down-regulated p27 protein expression is the possible underlying mechanism for the growth of uterine leiomyoma and over-expression of p27 induces cell death. This study provides better understanding of the control exerted by p27 in regulating growth and disease progression of uterine leiomyoma.
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Induction of Apoptosis by Hibiscus Protocatechuic Acid in Human Uterine Leiomyoma Cells
손원경,Sabarish Ramachandran,송대규,신소진,조치흠,권상훈,차순도 대한부인종양학회 2008 Journal of Gynecologic Oncology Vol.19 No.1
Objective: Hibiscus protocatechuic acid (PCA) is a food-derived polyphenol antioxidants used as a food additive and a traditional herbal medicine. In this study, PCA was to determine its effect on cell proliferation and cell cycle progression in primary cultured human uterine leiomyoma cells. Methods: The effect of PCA on cell proliferation and cell cycle progression was examined in the primary cultured human uterine leiomyoma cells. MTT reduction assay was carried out to determine the viability of uterine leiomyoma cells. Cell cycle analysis for Hibiscus protocatechuic acid treated leiomyoma cells was done by FACS analysis. DNA fragmentation assay was performed to determine fragmentation rate by PCA in leiomyoma cells. Western blot analysis was done using anti pRB, anti- p21cip1/waf1, anti- p53, anti-p27kip1, anti - cyclinE, anti CDK2 antibodies to detect the presence and expression of these proteins in PCA treated myoma cells. Results: PCA induced growth inhibition in a dose dependent manner, treatment with 5 mmol/L PCA blocked 80% cell growth. FACS results showed that there was increased the percentage of cells in sub G1. DNA fragmentation assay by ELISA was done to find the rate of apoptosis. Apoptosis took place but in a dose dependent manner. From Western blot analysis it revealed PCA induced the expression of p21cip1/waf1 and p27kip1 increasingly and was not mediated by p53. Caspase-7 pathway was activated and dephosphorylation of pRB took place. Conclusion: In Conclusions, PCA, a polyphenol antioxidant, inhibited cell proliferation and induced cell cycle arrest at sub G1 phase by enhancing the production of p21cip1/waf1 and p27kip1. These results indicate that PCA will be a promising agent for use in chemopreventive or therapeutics against human uterine leiomyoma.
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( Yoon Geon Kim ),( Sabarish Ramachandran ),( Dong Chul Kim ),( Young Bin Hong ),( Eun Ha Kim ),( Sang Hoon Kwon ),( So Jin Shin ),( Soon Do Cha ),( Insoo Bae ),( Chi Heum Cho ) 대한산부인과학회 2010 Journal of Womens Medicine Vol.3 No.3
Objective: To determine the anti-tumor effect of isoliquiritigenin (ISL) on endometrial cancer cell and to evaluate its effect on apoptosis in Hec1A endometrial cancer cell lines. Methods: Human endometrial cancer cell lines (Hec1A) and Ishikawa, and normal endometrial cell line (T-HESCS) were cultured in vitro. The viabilities of three cell lines on ISL were measured. Cell cycle distribution and induction of apoptosis were measured in Hec1A cells after ISL treatment. Results: ISL significantly reduced cell viabilities of endometrial cancer cell lines but not normal cell line in a dose-dependent manner. Cell cycle analysis indicated that ISL treatment increased the proportion of cells in the sub-G0/G1 phase. DNA fragmentation and fluorometric TUNEL assays also revealed apoptotic cell death after ISL incubation. ISL treatment markedly up-regulated the expression of cyclin-dependent kinase inhibitor, p21(Cip1/Waf1) in a p53 independent manner and down regulated the expressions of cyclins and CDKs, with concomitant increase in FAS and cleavage of caspase 7, caspase 8, and caspase 9. In addition, elevation of caspase 3 activity also observed in a dose and time dependent manner. Conclusion: ISL inhibited cell proliferation and triggered apoptosis in human endometrial cancer cell line Hec1A. Hence, ISL can be used as a potentially potent clinical chemotherapeutic agent for treating endometrial cancer.
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Jung Kyu Park,Chi Heum Cho,Sabarish Ramachandran,So Jin Shin,Sang Hoon Kwon,Sun Young Kwon,Soon Do Cha 대한암학회 2006 Cancer Research and Treatment Vol.38 No.2
Purpose: Sodium butyrate (NaBT) is principally a histonedeacetylase (HDAC) inhibitor, and it has the potentialto arrest HPV-positive carcinoma cells at the G1 toS phase transition of the cell cycle. The aim of study wasto determine whether phosphatidylinositol 3-kinase(PI3K) inhibition can enhance the inhibitory effect ofNaBT on a human cervical cancer cell line (HeLa).Materials and Methods: Cervical cancer cells (HeLa)were treated with NaBT alone or in combination with thePI3K inhibitors wortmannin or LY294002. Cell viabilityanalysis and FACS analysis were carried out. The expressionsof the cell cycle related proteins were evaluatedby Western-blot analysis.Results: Inhibition of PI3K enhanced NaBT-mediatedapoptosis and this decreased the HeLa cell viability.Either wortmannin or LY294002, combined with NaBT,enhanced the activation of caspase 3 and caspase 9, andthis enhanced the subsequent cleavage of poly (ADPribose)polymerase (PARP). Cervical cancer cells werearrested in the subG1 and G2/M phase, as was detectedby FACS analysis. NaBT treatment in combination withPI3K inhibitors showed the increased expression of theCDK inhibitors p21Cip1/Waf1 and p27Kip1, in a p53 dependentmanner, and also the increased dephosphorylation of Rbwhereas there was a reduction in the expression levelsof cyclin A, cyclin D1 and cyclin B1.Conclusion: The results demonstrate that inhibition ofPI3K enhances NaBT-mediated cervical cancer cell apoptosisthrough the activation of the caspase pathway.Moreover, these findings will support future investigationusing the PI3K inhibitors in combination with adjuvanttreatment for treating carcinoma of the cervix. (CancerRes Treat. 2006;38:112-117)
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