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

  • Authors:
    • Jong-Yun Kim
    • Hye-Eun Choi
    • Hwi-Ho Lee
    • Ji-Sun Shin
    • Dong‑Hyun Shin
    • Jung-Hye Choi
    • Yong Sup Lee
    • Kyung-Tae Lee
  • View Affiliations

  • Published online on: March 20, 2015     https://doi.org/10.3892/or.2015.3871
  • Pages: 2639-2647
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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 arrest. These results suggest that the 8-ADEQ inhibits the proliferation of human cervical cancer HeLa cells by DNA damage-mediated G2/M cell cycle arrest. 8-ADEQ‑induced G2/M arrest is mediated by the activation of both Chk1/2-Cdc25 and p53-p21CIP1/WAF1 via ATM/ATR pathway, and indicates that 8-ADEQ appears to have potential in the treatment of cervical cancer.
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May-2015
Volume 33 Issue 5

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Kim J, Choi H, Lee H, Shin J, Shin DH, Choi J, Lee YS and Lee K: 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 33: 2639-2647, 2015.
APA
Kim, J., Choi, H., Lee, H., Shin, J., Shin, D., Choi, J. ... Lee, K. (2015). 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. Oncology Reports, 33, 2639-2647. https://doi.org/10.3892/or.2015.3871
MLA
Kim, J., Choi, H., Lee, H., Shin, J., Shin, D., Choi, J., Lee, Y. S., Lee, K."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". Oncology Reports 33.5 (2015): 2639-2647.
Chicago
Kim, J., Choi, H., Lee, H., Shin, J., Shin, D., Choi, J., Lee, Y. S., Lee, K."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". Oncology Reports 33, no. 5 (2015): 2639-2647. https://doi.org/10.3892/or.2015.3871