The collective nuclear migration of p53 and phosphorylated S473 of Akt during ellipticine-mediated apoptosis in human lung epithelial cancer cells

Jing Ping Wang, Ya Chu Yu, Shih Ping Chen, Huan Chang Liang, Chia Wei Lin, Kang Fang

研究成果: 雜誌貢獻期刊論文同行評審

3 引文 斯高帕斯(Scopus)

摘要

Topoisomerase II inhibitor ellipticine effectively suppressed the growth of human non-small-cell-lung-cancer (NSCLC) epithelial cells. Previously, we reported the drug activity was consummated through parallel nucleus migration of p53 and Akt in A549 cells. While inducing cell death, the drug activity was proved related to autophagy through phosphorylated Akt at S473. In addition, ellipticine induced cytotoxicity in p53-null H1299 cells with stable expression of ectopic p53. In this work, we further demonstrated that dominant-negative AktS473A or p53 shRNA inhibited ellipticine-mediated translocalization of p53 and Akt and attenuated apoptotic cell death in A549 cells. The presence of p53 predates ellipticine-mediated apoptotic cell death, assists in nucleus translocation of phosphorylated Akt and activation of autophagy pathway. Growth inhibition through collaborating p53 and phosphorylated Akt473 in lung epithelial cancer cells provided a new perspective of the topoisomerase inhibitor as an effective cancer therapy agent.

原文英語
頁(從 - 到)123-133
頁數11
期刊Molecular and Cellular Biochemistry
407
發行號1-2
DOIs
出版狀態已發佈 - 2015 九月 17

ASJC Scopus subject areas

  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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