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Nuclear Translocation of Phosphorylated Akt is Critical in Ellipticine‐Induced Apoptosis in Human Lung Epithelial Cancer Cells A549
Author(s) -
Fang Kang,
Wang Jing-Ping,
Liang Huan-Chang,
Yu Ya-Chu,
Lin Kai-Han
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.553.1
Subject(s) - protein kinase b , apoptosis , a549 cell , phosphorylation , chemistry , cancer research , autophagy , transfection , microbiology and biotechnology , cancer cell , chromosomal translocation , programmed cell death , biology , cancer , biochemistry , gene , genetics
Topoisomerase II inhibitor ellipticine and its analogues were reported as promising antitumor agents. We have reported previously that ellipticine induced nuclear translocation of p53 and Akt followed by autophagic apoptosis in human non‐small cell lung cancer cells A549. The effect can be reverted by autophagy inhibitors. In this work, we further demonstrated that transfection of p53 siRNA suppressed ellipticine‐induced apoptosis by blocking Akt nuclear translocation. In addition, introduction of either point‐mutated Akt473 or Akt308 inhibited p53 translocation as indicated by confocal microscopy and western blotting. On the other hand, in p53‐null H1299 cells with stably expressed wild type p53, cells become sensitive to ellipticine treatment accompanied with nucleus translocation of p53 and Akt. In addition, as cells were pretreated with autophagy inhibitor before being treated with ellipticine, Akt phosphorylation was suppressed with decreased apoptotic cell death. We concluded nuclear translocation of phosphorylated Akt is essential in leading to ellipticine‐induced cell death in human non‐small cell lung cancer cells. The work is supported by grants from the National Science Council, Taiwan (NSC100‐2311‐B‐003‐003) and National Taiwan Normal University (99‐D3)