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JIN Hui, LIU Lifeng, DENG Weiping, LIU Jianwen. Antitumor effects and molecular mechanisms of novel selective HDAC inhibitors in human cervix carcinoma HeLa cells[J]. Journal of China Pharmaceutical University, 2013, 44(4): 352-356. DOI: 10.11665/j.issn.1000-5048.20130413
Citation: JIN Hui, LIU Lifeng, DENG Weiping, LIU Jianwen. Antitumor effects and molecular mechanisms of novel selective HDAC inhibitors in human cervix carcinoma HeLa cells[J]. Journal of China Pharmaceutical University, 2013, 44(4): 352-356. DOI: 10.11665/j.issn.1000-5048.20130413

Antitumor effects and molecular mechanisms of novel selective HDAC inhibitors in human cervix carcinoma HeLa cells

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  • Examine the antitumor activity of three new histone deacetylase(HDAC)and HDAC-1 inhibitors with the carboline structure named D16, D22, D29 and explore the molecular mechanisms underlying. The anti-proliferative effects were detected by MTT assays in MCF-7, HCT-116, A549, HeLa and K562. The inhibition in HDAC and HDAC-1 were detected by using fluorescent substrate. The effects on the cell cycle arrest and apoptosis induction were examined by flow cytometry. The protein expressions of acetylated-H3 and p21cip/WAF were detected by Western blotting. D16, D22, and D29 inhibited the proliferation of multiple carcinoma cells at much lower concentrations than SAHA dose-dependently. D16, D22, D29 effectively inhibited the activity of HDAC and HDAC-1; D16, D22 and D29 induced G1 phase cell cycle arrest and apoptosis while the protein expression of acetylation of histone H3 and p21cip/WAF were significantly up-regulated. D16, D22 and D29 were potent antitumor agents with their cycle arrest and apoptosis mechanisms. The molecualar mechanisms were associated with the promotion of acetylated-H3 and p21cip/WAF.
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