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

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)123-133
Number of pages11
JournalMolecular and Cellular Biochemistry
Volume407
Issue number1-2
DOIs
Publication statusPublished - 2015 Sep 17

Keywords

  • Akt
  • Apoptosis
  • Ellipticine
  • Human non-small-cell-lung-cancer cells
  • p53

ASJC Scopus subject areas

  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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