Resveratrol analogue (E)-8-acetoxy-2-[2-(3,4-diacetoxyphenyl)ethenyl]-quinazoline induces G2/M cell cycle arrest through the activation of ATM/ATR in human cervical carcinoma HeLa cells.

Resveratrol analogue (E)-8-acetoxy-2-[2-(3,4-diacetoxyphenyl)ethenyl]-quinazoline induces G2/M cell cycle arrest through the activation of ATM/ATR in human cervical carcinoma HeLa cells. Oncol Rep. 2015 May;33(5):2639-47 Authors: Kim JY, Choi HE, Lee HH, Shin JS, Shin DH, Choi JH, Lee YS, Lee KT Abstract Styrylquinazolines are synthetic analogues of resveratrol and have been suggested to cause anti-inflammatory activity by modulating prostaglandin E2 (PGE2) production. In the present study, we evaluated cytotoxic effects of various styrylquinazoline derivatives and found that (E)-8-acetoxy-2-[2-(3,4-diacetoxyphenyl)ethenyl]-quinazoline (8-ADEQ) most potently inhibited the proliferation of the human cervical carcinoma HeLa cells. Exploring the growth-inhibitory mechanisms of 8-ADEQ, we found that it causes a cell cycle arrest at the G2/M phase by DNA flow cytometric analysis, which was accompanied by upregulation of cyclin B1 expression and cyclin-dependent protein kinase 1 (Cdk1) phosphorylation. In addition, we observed that 8-ADEQ causes phosphorylation of the cell division cycle 25C (Cdc25C) protein through the activation of checkpoint kinases 1 (Chk1) and Chk2, which in turn were activated via ataxia telangiectasia mutated (ATM)/ataxia telangiectasia-Rad3-related (ATR) kinases in response to the DNA damage. Furthermore, ATM/ATR inhibitor caffeine, p53- or ATM/ATR-specific siRNA significantly attenuated 8-ADEQ-induced G2/M ar...
Source: Oncology Reports - Category: Cancer & Oncology Tags: Oncol Rep Source Type: research