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Identification of commonly regulated genes in HPV18-and HPV16-infected cervical cancer cells treated with the curcumin analogue 1,5-bis(2-hydroxyphenyl)-1,4-pentadiene-3-one

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Asian Pacific Journal of Tropical Biomedicine 2018年第1期8卷 44-51页

作者： Felicia Paulraj Faridah Abas Nordin H.Lajis Iekhsan Othman Sharifah Syed Hassan Rakesh Naidu Jeffrey Cheah School of Medicine & Health Sciences Monash University Malaysia Laboratory of Natural Products Faculty of Science Universiti Putra Malaysia Department of Food Science Faculty of Food Science and Technology Universiti Putra Malaysia

Objective: To identify commonly regulated genes in HPV-infected He La and Ca Ski cervical cancer cells treated with curcumin analogue 1,5-bis(2-hydroxyphenyl)-1,4-pentadiene-3-one(MS17) and to explore potential mechanisms that underlie its cytotoxic, anti-proliferative and apoptotic activity. Methods: He La and Ca Ski cells were treated with 2×EC50 and 3×EC50 doses of MS17 for 24 h and the RNA extracts were subjected to one-colour microarray-based gene expression profiling. Pair-wise significant genes(false discovery rate-corrected, P<0.05) were analysed for fold change(FC) compared to control samples. Differentially expressed genes with FC≥2.0(up-regulated; FC≥2.0 and down-regulated; FC≤-2.0) compared to the control samples were filtered through and analysed to create a global gene expression profile. Mutually regulated genes were ranked by FC and categorised by gene ontology. Results: Our data indicated dose-dependent regulation by MS17 and identified top 20 mutually upand down-regulated genes each in He La and Ca Ski cells. Amongst these 17 were commonly regulated in both cell lines. These include the up-regulation of CCL26, DEFB103 B, IL1 RL1, LY96, GCNT3, MMP10, MMP3, GADD45 G and HSPA6, and the down-regulation of TENM2, NEBL, KIFC1, CTDSP1, IGFBP5, LTBP1, NREP and MXD3. These genes were associated with key biological functions that were proposed to mediate the anticancer activity of MS17 in cervical cancer cells such as immune response, metabolic processes, proteolysis, programmed cell death, unfolded protein response, cell adhesion, cytoskeletal organisation, phosphatase activity, signal transduction and transcription regulator activity. Conclusions: Identification of seventeen common genes modulated by MS17 could be used as potential therapeutic targets in both cervical cancer cell lines and the findings of this study could be used to present an insight into the potential antitumor activity of MS17 in cervical cancer.

关键词： Diarylpentanoid Cervical cancer Gene expression profiling Microarray curcumin analogue

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Synergistic effects of a curcumin analogue and docetaxel on growth inhibition of human prostate cancer cells

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Journal of Chinese Pharmaceutical Sciences 2017年第11期26卷 827-833页

作者：周代营丁立王希马娟黄沃林 Susan Goodin 郑希广东食品药品职业学院广东广州510520 美国新泽西罗格斯癌症研究所美国罗格斯大学苏珊Lehman Cullman癌症研究所

Cancer of the prostate gland is a leading cause of death. In the present study, we studied the effects and mechanisms of curcumin analogue E10, docetaxel or their combination on prostate cancer （PC）-3 cells. Treatment of PC-3 cells with El0 or docetaxel resulted in growth inhibition in a concentration-reliant fashion. Combinations of E10 and docetaxel inhibited the growth of PC-3 cells in a synergistic manner. Effects of a combination of E10 and docetaxel were associated with synergistic inhibition of the transcriptional activity of nuclear factor-kappa B （NF-KB）, and robust reductions in the levels of B-cell lymphoma-2 （Bcl-2） were found in PC-3 cells treated with a combination of E10 and docetaxel. Our data indicated that the effects of El0 in combination with docetaxel on PC-3 cells were associated with inhibition of NF-r,B and Bcl-2. Further studies using suitable animal models are necessary to determine the in vivo effect of this combination.

关键词： Combination treatment Prostate cancer curcumin analogue Docetaxel Synergistic effect

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