title: Plumbagin induces apoptotic and autophagic cell death through inhibition of the PI3K/Akt/mTOR pathway in human non-small cell lung cancer cells.
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.
authors.affiliation: 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.
authors.forename: Yan-Cong
authors.initials: YC
authors.lastname: Li
authors.affiliation: Department of Obstetrics and Gynecology, Xiaolan Hospital, Southern Medical University, Zhongshan, Guangdong 528415, China.
authors.forename: Shu-Ming
authors.initials: SM
authors.lastname: He
authors.affiliation: 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.
authors.forename: Zhi-Xu
authors.initials: ZX
authors.lastname: He
authors.affiliation: Department of Pharmaceutical Science, College of Pharmacy, University of South Florida, Tampa, FL 33612, USA.
authors.forename: Minghua
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Hepatobiliary Surgery, General Hospital of Ningxia Medical University, Yinchuan City, Ningxia Hui Autonomous Region 750004, China.
authors.forename: Yinxue
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Center of Drug Evaluation and Research, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.
authors.forename: Jian-Xin
authors.initials: JX
authors.lastname: Pang
authors.affiliation: Research Center for Bioengineering and Sensing Technology, University of Science and Technology Beijing, Beijing 100083, China.
authors.forename: Xueji
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutical Science, College of Pharmacy, University of South Florida, Tampa, FL 33612, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Chow
authors.affiliation: Department of Pharmaceutical Science, College of Pharmacy, University of South Florida, Tampa, FL 33612, USA.
authors.forename: Qingyu
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: School of Medicine, Deakin University, Waurn Ponds, Victoria 3217, Australia.
authors.forename: Wei
authors.initials: W
authors.lastname: Duan
authors.affiliation: Department of Pharmaceutical Science, College of Pharmacy, University of South Florida, Tampa, FL 33612, USA.
authors.forename: Zhi-Wei
authors.initials: ZW
authors.lastname: Zhou
authors.affiliation: Department of Internal Medicine, University of Utah and Salt Lake Veterans Affairs Medical Center, Salt Lake City, UT, USA.
authors.forename: Tianxin
authors.initials: T
authors.lastname: Yang
authors.affiliation: Department of Gastroenterology, the First Affiliated Hospital of Guangxi Traditional Chinese Medical University, Nanning 530011, Guangxi Zhuang Autonomous Region, China.
authors.forename: Gui-Hua
authors.initials: GH
authors.lastname: Huang
authors.affiliation: Medical Research Center, General Hospital of Chinese People's Armed Police Forces (CAPF), 69 Yongding Road, Beijing 100039, China.
authors.forename: Aibing
authors.initials: A
authors.lastname: Liu
authors.affiliation: Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, China. Electronic address: qiujiaxuan@163.com.
authors.forename: Jia-Xuan
authors.initials: JX
authors.lastname: Qiu
authors.affiliation: 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.
authors.forename: Jun-Ping
authors.initials: JP
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Shu-Feng
authors.initials: SF
authors.lastname: Zhou
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D009285:Naphthoquinones / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D009285:Naphthoquinones; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; C546842:MTOR protein, human; C014758:plumbagin
keywords: Apoptosis; Autophagy; Non-small-cell lung cancer; PI3K/Akt/mTOR; Plumbagin