title: Ophiopogonin B-induced autophagy in non-small cell lung cancer cells             via inhibition of the PI3K/Akt signaling pathway.
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.
authors.affiliation: The Pre-clinical Medicine College, Nanjing University of Chinese Medicine, Nanjing 210046, PR China.
authors.forename: Meijuan
authors.initials: M
authors.lastname: Chen
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Du
authors.forename: Min
authors.initials: M
authors.lastname: Qui
authors.forename: Mingyan
authors.initials: M
authors.lastname: Wang
authors.forename: Kejun
authors.initials: K
authors.lastname: Chen
authors.forename: Zhenzhou
authors.initials: Z
authors.lastname: Huang
authors.forename: Miao
authors.initials: M
authors.lastname: Jiang
authors.forename: Fei
authors.initials: F
authors.lastname: Xiong
authors.forename: Jianping
authors.initials: J
authors.lastname: Chen
authors.forename: Jing
authors.initials: J
authors.lastname: Zhou
authors.forename: Fengrong
authors.initials: F
authors.lastname: Jiang
authors.forename: Lian
authors.initials: L
authors.lastname: Yin
authors.forename: Yuping
authors.initials: Y
authors.lastname: Tang
authors.forename: Lihong
authors.initials: L
authors.lastname: Ye
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhan
authors.forename: Jin-Αo
authors.initials: JΑ
authors.lastname: Duan
authors.forename: Hai-Αn
authors.initials: HΑ
authors.lastname: Fu
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
mesh_terms: D001343:Autophagy / Q000187:drug effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000201:enzymology; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003593:Cytoplasm; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012503:Saponins / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D013150:Spirostans / Q000494:pharmacology*; D014617:Vacuoles / Q000187:drug effects
chemical_list: C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D010936:Plant Extracts; D012503:Saponins; D013150:Spirostans; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C046997:ophiopogonin B