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A novel dithiocarbamate derivative induces cell apoptosis through p53-dependent intrinsic pathway and suppresses the expression of the E6 oncogene of human papillomavirus 18 in HeLa cells
Li, YH (Li, Yanhong); Qi, HX (Qi, Hongxue); Li, XB (Li, Xiaobo); Hou, XL (Hou, Xueling); Lu, XY (Lu, Xueying); Xiao, XW (Xiao, Xiangwen)
2015
Source PublicationAPOPTOSIS
ISSN1360-8185
Volume20Issue:6Pages:787-795
Abstract

Dithiocarbamates (DTCs) exhibit a broad spectrum of antitumor activities, however, their molecular mechanisms of antitumor have not yet been elucidated. Previously, we have synthesized a series of novel dithiocarbamate derivatives. These DTCs were examined for cytotoxic activities against five human cancer cell lines. In this study, one of dithiocarbamate (DTC1) with higher potential for HeLa cells was chosen to investigate molecular mechanisms for its anti-tumor activities. DTC1 could inhibit proliferation, and highly induce apoptosis in HeLa cells by activating caspase-3, -6 and -9; moreover, activities of caspase-3, -6 and -9 were inhibited by pan-caspase inhibitor, Z-VAD-FMK. Furthermore, DTC1 decreased the levels of Bcl-2 and Bcl-xL, and increased expression of cytosol cytochrome c, Bak, Bax and p53 in a time-dependent manner but had no effect on the level of Rb. It was shown that DTC1 induced HeLa cells apoptosis through a p53-dependent pathway as tested by the wild type p53 inhibitor, pifithrin-alpha. Additionally, the relative expression of E6 and E7 were evaluated in HPV18-positive (HeLa cells) by real-time PCR and western blotting. The results firstly demonstrated that DTC1 suppressed both expression of E6 mRNA and E6 oncoprotein, but had no effect on the expression of E7 mRNA and protein in HPV18. Our results suggested that DTC1 may serve as novel chemotherapeutic agents in the treatment of cervical cancer and potential anti-HPV virus candidates that merit further studies.

KeywordDithiocarbamate Derivative Apoptosis Caspase P53-dependent Intrinsic Pathway Hpv18 E6
DOI10.1007/s10495-015-1114-4
Indexed BySCI
WOS IDWOS:000352789700003
Citation statistics
Cited Times:11[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.xjipc.cas.cn/handle/365002/4296
Collection省部共建新疆特有药用资源利用重点实验室
资源化学研究室
AffiliationChinese Acad Sci, Xinjiang Tech Inst Phys & Chem, Key Lab Chem Plant Resources Arid Reg, Urumqi 830011, Peoples R China
Recommended Citation
GB/T 7714
Li, YH ,Qi, HX ,Li, XB ,et al. A novel dithiocarbamate derivative induces cell apoptosis through p53-dependent intrinsic pathway and suppresses the expression of the E6 oncogene of human papillomavirus 18 in HeLa cells[J]. APOPTOSIS,2015,20(6):787-795.
APA Li, YH ,Qi, HX ,Li, XB ,Hou, XL ,Lu, XY ,&Xiao, XW .(2015).A novel dithiocarbamate derivative induces cell apoptosis through p53-dependent intrinsic pathway and suppresses the expression of the E6 oncogene of human papillomavirus 18 in HeLa cells.APOPTOSIS,20(6),787-795.
MLA Li, YH ,et al."A novel dithiocarbamate derivative induces cell apoptosis through p53-dependent intrinsic pathway and suppresses the expression of the E6 oncogene of human papillomavirus 18 in HeLa cells".APOPTOSIS 20.6(2015):787-795.
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