Ophiopogonin B-induced autophagy in non-small cell lung cancer cells via inhibition of the PI3K/Akt signaling pathway

• Type of Material: Article
• Authors: Meijuan Chen, Nanjing University; Yuhong Du, Emory University; Min Qui, Emory University; Mingyan Wang, Nanjing University; Kejun Chen, Emory University; Zhenzhou Huang, Nanjing University; Miao Jiang, Nanjing University; Fei Xiong, Nanjing University; Jianping Chen, Nanjing University; Jing Zhou, Nanjing University; Fengrong Jiang, Nanjing University; Lian Yin, Nanjing University; Yuping Tang, Nanjing University; Lihong Ye, Nanjing University; Zhen Zhan, Nanjing University; Jin-Ao Duan, Nanjing University; Haian Fu, Emory University; Xu Zhang, Nanjing University
• Language: English
• Date: 2012-11-09
• Publisher: Spandidos Publications
• Publication Version: Final Published Version
• Copyright Statement: © 2013, Spandidos Publications
• License: Creative Commons Attribution-Noncommercial 3.0 Unported
• Final Published Version (URL): http://www.spandidos-publications.com/10.3892/or.2012.2131
• Title of Journal or Parent Work: Oncology Reports
• ISSN: 1021-335X
• Volume: 29
• Issue: 2
• Start Page: 430
• End Page: 436
• Grant/Funding Information: This study was supported in part by National Science and Technology Pillar Program in the 11th Five-year Plan of China 2006BAI11B08-01 (to H.F. and X.Z), the Priority Academic Program Development (PAPD) of Jiangsu Higher Education Institutions (to X.Z), the Research and Innovation Program of Postgraduates in Jiangsu Province (to M.C.).
• Keywords: natural medicines; Ophiopogonin B; autophagy; non-small cell lung cancer; PI3K/Akt/mTOR
• Research Categories: Health Sciences, Pharmacology; Health Sciences, Oncology

Abstract

Ophiopogonin B (OP-B) is a bioactive component of Radix Ophiopogon Japonicus, which is often used in Chinese traditional medicine to treat pulmonary disease. However, whether or not OP-B has any potential antitumor activity has not been reported. Here, we show that the non-small cell lung cancer (NSCLC) cell lines NCI-H157 and NCI-H460 treated with OP-B grow more slowly and accumulate vacuoles in their cytoplasm compared to untreated control cells. Flow cytometric analysis showed that the cells were arrested in G0/G1 phase. Nuclear morphology, Annexin-V/PI staining, and expression of cleaved caspase-3 all confirm that OP-B does not induce apoptosis. Instead, based on results from both transmission electron microscopy (TEM) and the expression of microtubule-associated protein 1 light chain 3-II (LC3-II), we determined that OP-B treatment induced autophagy in both cell lines. Next, we examined the PI3K/Akt/mTOR signaling pathway and found that OP-B inhibited phosphorylation of Akt (Ser473, Thr308) in NCI-H157 cells and also inhibited several key components of the pathway in NCI-H460 cells, such as p-Akt(Ser473, Thr308), p-p70S6K (Thr389). Additionally, insulin-mediated activation of the PI3K/Akt/mTOR pathway provides evidence that activation of this pathway may correlate with induction of autophagy in H460 cells. Therefore, OP-B is a prospective inhibitor of PI3K/Akt and may be used as an alternative compound to treat NSCLC.