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

被引：202

作者：

Li, Yan-Cong ^{[1
,2
]}

He, Shu-Ming ^{[3
]}

He, Zhi-Xu

Li, Minghua ^{[2
]}

Yang, Yinxue ^{[6
]}

Pang, Jian-Xin ^{[7
]}

Zhang, Xueji ^{[8
]}

Chow, Kevin ^{[2
]}

Zhou, Qingyu ^{[2
]}

Duan, Wei ^{[9
]}

Zhou, Zhi-Wei ^{[2
]}

Yang, Tianxin ^{[10
,11
]}

Huang, Gui-Hua ^{[12
]}

Liu, Aibing ^{[13
]}

Qiu, Jia-Xuan ^{[14
]}

Liu, Jun-Ping ^{[15
,16
,17
]}

Zhou, Shu-Feng ^{[2
,4
,5
]}

机构：

[1] Southern Med Univ, Xiaolan Hosp, Dept Resp Med, Zhongshan 528415, Guangdong, Peoples R China

[2] Univ S Florida, Coll Pharm, Dept Pharmaceut Sci, Tampa, FL 33612 USA

[3] Southern Med Univ, Xiaolan Hosp, Dept Obstet & Gynecol, Zhongshan 528415, Guangdong, Peoples R China

[4] Guiyang Med Univ, Stem Cell & Tissue Engn Res Ctr, Guizhou Prov Key Lab Regenerat Med, Guiyang 550004, Guizhou, Peoples R China

[5] Guiyang Med Univ, Sino US Joint Lab Med Sci, Guiyang 550004, Guizhou, Peoples R China

[6] Ningxia Med Univ, Dept Hepatobiliary Surg, Gen Hosp, Yinchuan City 750004, Ningxia Hui Aut, Peoples R China

[7] Southern Med Univ, Sch Pharmaceut Sci, Ctr Drug Evaluat & Res, Guangzhou 510515, Guangdong, Peoples R China

[8] Univ Sci & Technol Beijing, Res Ctr Bioengn & Sensing Technol, Beijing 100083, Peoples R China

[9] Deakin Univ, Sch Med, Geelong, Vic 3217, Australia

[10] Univ Utah, Dept Internal Med, Salt Lake City, UT 84112 USA

[11] Salt Lake Vet Affairs Med Ctr, Salt Lake City, UT 84112 USA

[12] Guangxi Tradit Chinese Med Univ, Dept Gastroenterol, Affiliated Hosp 1, Nanning, Guangxi Zhuang 530011, Peoples R China

[13] Chinese Peoples Armed Police Forces CAPF, Gen Hosp, Med Res Ctr, Beijing 100039, Peoples R China

[14] Nanchang Univ, Dept Oral & Maxillofacial Surg, Affiliated Hosp 1, Nanchang 330006, Jiangxi, Peoples R China

[15] Hangzhou Normal Univ, Inst Ageing Res, Sch Med, Hangzhou, Zhejiang, Peoples R China

[16] Monash Univ, Cent Clin Sch, Dept Immunol, Prahran, Vic, Australia

[17] Univ Melbourne, Dept Genet, Parkville, Vic 3052, Australia

来源：

CANCER LETTERS | 2014年 / 344卷 / 02期

关键词：

Plumbagin; Non-small-cell lung cancer; Apoptosis; Autophagy; PI3K/Akt/mTOR; NF-KAPPA-B; CYTOCHROME-C; CYCLE ARREST; IN-VITRO; SIGNALING PATHWAY; BONE METASTASIS; P53; BREAST; PHOSPHORYLATION; EXPRESSION;

D O I：

10.1016/j.canlet.2013.11.001

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

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. (C) 2013 Elsevier Ireland Ltd. All rights reserved.

引用

页码：239 / 259

页数：21

共 69 条

[1]

Plumbagin-Induced Apoptosis of Human Breast Cancer Cells Is Mediated by Inactivation of NF-κB and Bcl-2 [J].