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 : an International Journal on Programmed Cell Death
Yanhong LiXiangwen Xiao

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-α. 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 onc...Continue Reading

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Citations

Jun 6, 2016·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Yang-Yang HanJin-Ming Gao
Sep 5, 2020·Pharmaceuticals·Aleksandra HecelMagdalena Rowińska-Żyrek
Nov 29, 2017·Proceedings of the National Academy of Sciences of the United States of America·Hong GaoFudi Wang
Dec 14, 2017·Nature Communications·Lu YangYuesheng Zhang
Feb 9, 2021·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Pit Foong ChanRoslida Abd Hamid

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