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Non-toxic dose chidamide synergistically enhances platinum-induced DNA damage responses and apoptosis in Non-Small-Cell lung cancer cells
Zhou, You1,2; Pan, De-Si2; Shan, Song2; Zhu, Jing-Zhong2; Zhang, Kun2; Yue, Xu-Peng2; Nie, Li-Ping3; Wan, Jun1; Lu, Xian-Ping2; Zhang, Wei1; Ning, Zhi-Qiang2
关键词HDAC inhibitor Carboplatin Cisplatin Oxaliplatin DNA damage Non-small-cell lung cancer
刊名BIOMEDICINE & PHARMACOTHERAPY
2014-05-01
DOI10.1016/j.biopha.2014.03.011
68期:4页:483-491
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Medicine, Research & Experimental ; Pharmacology & Pharmacy
研究领域[WOS]Research & Experimental Medicine ; Pharmacology & Pharmacy
关键词[WOS]HISTONE DEACETYLASE INHIBITORS ; DOUBLE-STRAND BREAKS ; CARCINOMA-CELLS ; OVARIAN-CANCER ; CYCLE ARREST ; ANTITUMOR-ACTIVITY ; TRICHOSTATIN-A ; PHASE-II ; IN-VIVO ; CYTOTOXICITY
英文摘要

Combination of low doses of histone deacetylases inhibitors and chemotherapy drugs is considered as one of the most promising strategies to increase the anticancer efficacy. Chidamide is a novel benzamide chemical class of HDAC inhibitor that selectively inhibited HDAC1, 2, 3 and 10. We sought to determine whether chidamide may enhance platinum-induced cytotoxicity in NSCLC cells. In this study, the combination of chidamide with carboplatin showed a good synergism on growth inhibition with the mean combination index value as 0.712 and 0.639 in A549 and NCI-H157 cells, respectively. The used concentration of chidamide was non-toxic on cells by itself as low as 0.3 mu M. All of our experiments were comparisons between combination regimen and single carboplatin regimen in A549 and NCI-H157 cell lines. Phosphorylated histone H2A. X (gamma H2AX), a hall marker of DNA damage response, was dramatically increased by the combination treatment. Cell cycle analysis by flow cytometry and phosphorylation level analysis of histone H3 (Ser10) by western blotting showed that combination treatment significantly increased the percentage of G2/M phase of cells. Mitochondrial membrane potential and cleaved-PARP1 level analysis indicate that chidamide synergistically enhances carboplatin-induced apoptosis. Additionally, synergistic effects of chidamide were found when it was combined with two other platinum drugs (cisplatin and oxaliplatin). The results suggest that Chidamide in combination with platinum drugs may be a novel therapeutic option for NSCLC. (C) 2014 Elsevier Masson SAS. All rights reserved.

语种英语
WOS记录号WOS:000336538400013
引用统计
被引频次:28[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/67026
专题北京大学深圳医院
作者单位1.Shenzhen PKU HKUST Med Ctr, Biomed Res Inst, Shenzhen 518036, Guangdong, Peoples R China
2.Chipscreen Biosci Ltd, Shenzhen 518057, Guangdong, Peoples R China
3.Peking Univ, Shenzhen Hosp, Dept Clin Lab, Beijing, Guangdong, Peoples R China
推荐引用方式
GB/T 7714
Zhou, You,Pan, De-Si,Shan, Song,et al. Non-toxic dose chidamide synergistically enhances platinum-induced DNA damage responses and apoptosis in Non-Small-Cell lung cancer cells[J]. BIOMEDICINE & PHARMACOTHERAPY,2014,68(4):483-491.
APA Zhou, You.,Pan, De-Si.,Shan, Song.,Zhu, Jing-Zhong.,Zhang, Kun.,...&Ning, Zhi-Qiang.(2014).Non-toxic dose chidamide synergistically enhances platinum-induced DNA damage responses and apoptosis in Non-Small-Cell lung cancer cells.BIOMEDICINE & PHARMACOTHERAPY,68(4),483-491.
MLA Zhou, You,et al."Non-toxic dose chidamide synergistically enhances platinum-induced DNA damage responses and apoptosis in Non-Small-Cell lung cancer cells".BIOMEDICINE & PHARMACOTHERAPY 68.4(2014):483-491.
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