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Cancer Lett. 2014 Mar 28;344(2):239-59. doi: 10.1016/j.canlet.2013.11.001. Epub 2013 Nov 23.

Plumbagin induces apoptotic and autophagic cell death through inhibition of the PI3K/Akt/mTOR pathway in human non-small cell lung cancer cells.

Author information

1
Department of Respiratory Medicine, Xiaolan Hospital, Southern Medical University, Zhongshan, Guangdong 528415, China; Department of Pharmaceutical Science, College of Pharmacy, University of South Florida, Tampa, FL 33612, USA.
2
Department of Obstetrics and Gynecology, Xiaolan Hospital, Southern Medical University, Zhongshan, Guangdong 528415, China.
3
Guizhou Provincial Key Laboratory for Regenerative Medicine, Stem Cell and Tissue Engineering Research Center & Sino-US Joint Laboratory for Medical Sciences, Guiyang Medical University, Guiyang 550004, Guizhou, China.
4
Department of Pharmaceutical Science, College of Pharmacy, University of South Florida, Tampa, FL 33612, USA.
5
Department of Hepatobiliary Surgery, General Hospital of Ningxia Medical University, Yinchuan City, Ningxia Hui Autonomous Region 750004, China.
6
Center of Drug Evaluation and Research, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.
7
Research Center for Bioengineering and Sensing Technology, University of Science and Technology Beijing, Beijing 100083, China.
8
School of Medicine, Deakin University, Waurn Ponds, Victoria 3217, Australia.
9
Department of Internal Medicine, University of Utah and Salt Lake Veterans Affairs Medical Center, Salt Lake City, UT, USA.
10
Department of Gastroenterology, the First Affiliated Hospital of Guangxi Traditional Chinese Medical University, Nanning 530011, Guangxi Zhuang Autonomous Region, China.
11
Medical Research Center, General Hospital of Chinese People's Armed Police Forces (CAPF), 69 Yongding Road, Beijing 100039, China.
12
Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, China. Electronic address: qiujiaxuan@163.com.
13
Institute of Ageing Research, Hangzhou Normal University School of Medicine, Hangzhou, China; Department of Immunology, Monash University Central Clinical School, Prahran, Victoria, Australia; Department of Genetics, The University of Melbourne, Parkville, Victoria 3052, Australia.
14
Department of Pharmaceutical Science, College of Pharmacy, University of South Florida, Tampa, FL 33612, USA; Guizhou Provincial Key Laboratory for Regenerative Medicine, Stem Cell and Tissue Engineering Research Center & Sino-US Joint Laboratory for Medical Sciences, Guiyang Medical University, Guiyang 550004, Guizhou, China. Electronic address: shufengzhou2006@hotmail.com.

Abstract

Plumbagin (PLB) has shown anti-cancer activity but the mechanism is unclear. This study has found that PLB has a potent pro-apoptotic and pro-autophagic effect on A549 and H23 cells. PLB arrests cells in G2/M phase, and increases the intracellular level of reactive oxygen species in both cell lines. PLB dose-dependently induces autophagy through inhibition of PI3K/Akt/mTOR pathway as indicated by reduced phosphorylation of Akt and mTOR. Inhibition or induction of autophagy enhances PLB-induced apoptosis. There is crosstalk between PLB-induced apoptosis and autophagy. These findings indicate that PLB initiates both apoptosis and autophagy in NSCLC cells through coordinated pathways.

KEYWORDS:

Apoptosis; Autophagy; Non-small-cell lung cancer; PI3K/Akt/mTOR; Plumbagin

PMID:
24280585
DOI:
10.1016/j.canlet.2013.11.001
[Indexed for MEDLINE]

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