Ellipticine-induced apoptosis depends on Akt translocation and signaling in lung epithelial cancer cells

Kang Fang, Shih Ping Chen, Chia Wei Lin, Wan Chun Cheng, Hwei Tien Huang

研究成果: 雜誌貢獻文章

24 引文 (Scopus)

摘要

Ellipticine and its analogues were reported as topoisomerase II inhibitors and promising antitumor agents. In this work, we showed that the growth of human non-small-cell-lung-cancer (NSCLC) epithelial cells A549 can be inhibited by ellipticine. The inhibitory effect was reverted by PI3K inhibitors. The sub-G 1 phase cells after ellipticine treatment appeared at the expense of those that accumulated first at S- and G 2 /M phases during the early stage of treatment. We showed that the progression leading to cell death was impaired by wortmannin, which reverted apoptosis by retaining cells at S- and G 2 /M transition states. The characteristic apoptosis marker p53 activation after treatment appeared first followed by poly(ADP-ribose)polymerase (PARP) fragmentation. They disappeared upon co-treatment with wortmannin and the apoptotic phenotype reversed. Furthermore, ellipticine regulated endogenous survival signaling by up-regulating phosphorylated Akt that returned to its basal level later. Furthermore, ellipticine induced nucleus translocalization of p53 and Akt and recruitment of autophagosomes. The autophagic-related cell death was interfered by wortmannin and the suppressed growth reverted. The Akt-related cell death also occurred in p53-deficient cells with stable expression of exogenous p53. The work showed that ellipticine-induced cytotoxicity in NSCLC cells was achieved through autophagy and apoptotic death as a result of Akt-modulation. Being a topoisomerase II inhibitor, ellipticine proved a regulator in autophagy-related cell death through corporation of p53 and Akt.

原文英語
頁(從 - 到)227-234
頁數8
期刊Lung Cancer
63
發行號2
DOIs
出版狀態已發佈 - 2009 二月

指紋

ellipticine
Lung Neoplasms
Epithelial Cells
Apoptosis
Autophagy
Topoisomerase II Inhibitors
Cell Death
Non-Small Cell Lung Carcinoma
Poly(ADP-ribose) Polymerases
Growth
Phosphatidylinositol 3-Kinases
Cell Division
Antineoplastic Agents

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

引用此文

Ellipticine-induced apoptosis depends on Akt translocation and signaling in lung epithelial cancer cells. / Fang, Kang; Chen, Shih Ping; Lin, Chia Wei; Cheng, Wan Chun; Huang, Hwei Tien.

於: Lung Cancer, 卷 63, 編號 2, 02.2009, p. 227-234.

研究成果: 雜誌貢獻文章

Fang, Kang ; Chen, Shih Ping ; Lin, Chia Wei ; Cheng, Wan Chun ; Huang, Hwei Tien. / Ellipticine-induced apoptosis depends on Akt translocation and signaling in lung epithelial cancer cells. 於: Lung Cancer. 2009 ; 卷 63, 編號 2. 頁 227-234.
@article{a8e3da445c89438cb6923c6ff27181fc,
title = "Ellipticine-induced apoptosis depends on Akt translocation and signaling in lung epithelial cancer cells",
abstract = "Ellipticine and its analogues were reported as topoisomerase II inhibitors and promising antitumor agents. In this work, we showed that the growth of human non-small-cell-lung-cancer (NSCLC) epithelial cells A549 can be inhibited by ellipticine. The inhibitory effect was reverted by PI3K inhibitors. The sub-G 1 phase cells after ellipticine treatment appeared at the expense of those that accumulated first at S- and G 2 /M phases during the early stage of treatment. We showed that the progression leading to cell death was impaired by wortmannin, which reverted apoptosis by retaining cells at S- and G 2 /M transition states. The characteristic apoptosis marker p53 activation after treatment appeared first followed by poly(ADP-ribose)polymerase (PARP) fragmentation. They disappeared upon co-treatment with wortmannin and the apoptotic phenotype reversed. Furthermore, ellipticine regulated endogenous survival signaling by up-regulating phosphorylated Akt that returned to its basal level later. Furthermore, ellipticine induced nucleus translocalization of p53 and Akt and recruitment of autophagosomes. The autophagic-related cell death was interfered by wortmannin and the suppressed growth reverted. The Akt-related cell death also occurred in p53-deficient cells with stable expression of exogenous p53. The work showed that ellipticine-induced cytotoxicity in NSCLC cells was achieved through autophagy and apoptotic death as a result of Akt-modulation. Being a topoisomerase II inhibitor, ellipticine proved a regulator in autophagy-related cell death through corporation of p53 and Akt.",
keywords = "Akt, Apoptosis, Ellipticine, Human non-small-cell-lung-cancer cells",
author = "Kang Fang and Chen, {Shih Ping} and Lin, {Chia Wei} and Cheng, {Wan Chun} and Huang, {Hwei Tien}",
year = "2009",
month = "2",
doi = "10.1016/j.lungcan.2008.05.026",
language = "English",
volume = "63",
pages = "227--234",
journal = "Lung Cancer",
issn = "0169-5002",
publisher = "Elsevier Ireland Ltd",
number = "2",

}

TY - JOUR

T1 - Ellipticine-induced apoptosis depends on Akt translocation and signaling in lung epithelial cancer cells

AU - Fang, Kang

AU - Chen, Shih Ping

AU - Lin, Chia Wei

AU - Cheng, Wan Chun

AU - Huang, Hwei Tien

PY - 2009/2

Y1 - 2009/2

N2 - Ellipticine and its analogues were reported as topoisomerase II inhibitors and promising antitumor agents. In this work, we showed that the growth of human non-small-cell-lung-cancer (NSCLC) epithelial cells A549 can be inhibited by ellipticine. The inhibitory effect was reverted by PI3K inhibitors. The sub-G 1 phase cells after ellipticine treatment appeared at the expense of those that accumulated first at S- and G 2 /M phases during the early stage of treatment. We showed that the progression leading to cell death was impaired by wortmannin, which reverted apoptosis by retaining cells at S- and G 2 /M transition states. The characteristic apoptosis marker p53 activation after treatment appeared first followed by poly(ADP-ribose)polymerase (PARP) fragmentation. They disappeared upon co-treatment with wortmannin and the apoptotic phenotype reversed. Furthermore, ellipticine regulated endogenous survival signaling by up-regulating phosphorylated Akt that returned to its basal level later. Furthermore, ellipticine induced nucleus translocalization of p53 and Akt and recruitment of autophagosomes. The autophagic-related cell death was interfered by wortmannin and the suppressed growth reverted. The Akt-related cell death also occurred in p53-deficient cells with stable expression of exogenous p53. The work showed that ellipticine-induced cytotoxicity in NSCLC cells was achieved through autophagy and apoptotic death as a result of Akt-modulation. Being a topoisomerase II inhibitor, ellipticine proved a regulator in autophagy-related cell death through corporation of p53 and Akt.

AB - Ellipticine and its analogues were reported as topoisomerase II inhibitors and promising antitumor agents. In this work, we showed that the growth of human non-small-cell-lung-cancer (NSCLC) epithelial cells A549 can be inhibited by ellipticine. The inhibitory effect was reverted by PI3K inhibitors. The sub-G 1 phase cells after ellipticine treatment appeared at the expense of those that accumulated first at S- and G 2 /M phases during the early stage of treatment. We showed that the progression leading to cell death was impaired by wortmannin, which reverted apoptosis by retaining cells at S- and G 2 /M transition states. The characteristic apoptosis marker p53 activation after treatment appeared first followed by poly(ADP-ribose)polymerase (PARP) fragmentation. They disappeared upon co-treatment with wortmannin and the apoptotic phenotype reversed. Furthermore, ellipticine regulated endogenous survival signaling by up-regulating phosphorylated Akt that returned to its basal level later. Furthermore, ellipticine induced nucleus translocalization of p53 and Akt and recruitment of autophagosomes. The autophagic-related cell death was interfered by wortmannin and the suppressed growth reverted. The Akt-related cell death also occurred in p53-deficient cells with stable expression of exogenous p53. The work showed that ellipticine-induced cytotoxicity in NSCLC cells was achieved through autophagy and apoptotic death as a result of Akt-modulation. Being a topoisomerase II inhibitor, ellipticine proved a regulator in autophagy-related cell death through corporation of p53 and Akt.

KW - Akt

KW - Apoptosis

KW - Ellipticine

KW - Human non-small-cell-lung-cancer cells

UR - http://www.scopus.com/inward/record.url?scp=58049195157&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=58049195157&partnerID=8YFLogxK

U2 - 10.1016/j.lungcan.2008.05.026

DO - 10.1016/j.lungcan.2008.05.026

M3 - Article

C2 - 18619705

AN - SCOPUS:58049195157

VL - 63

SP - 227

EP - 234

JO - Lung Cancer

JF - Lung Cancer

SN - 0169-5002

IS - 2

ER -