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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.
AuthorsMeijuan Chen, Yuhong Du, Min Qui, Mingyan Wang, Kejun Chen, Zhenzhou Huang, Miao Jiang, Fei Xiong, Jianping Chen, Jing Zhou, Fengrong Jiang, Lian Yin, Yuping Tang, Lihong Ye, Zhen Zhan, Jin-Αo Duan, Hai-Αn Fu, Xu Zhang
JournalOncology reports (Oncol Rep) Vol. 29 Issue 2 Pg. 430-6 (Feb 2013) ISSN: 1791-2431 [Electronic] Greece
PMID23151908 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • MAP1LC3A protein, human
  • Microtubule-Associated Proteins
  • Plant Extracts
  • Saponins
  • Spirostans
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • ophiopogonin B
Topics
  • Autophagy (drug effects)
  • Carcinoma, Non-Small-Cell Lung (drug therapy, enzymology)
  • Cell Cycle Checkpoints (drug effects)
  • Cell Line, Tumor
  • Cell Proliferation (drug effects)
  • Cytoplasm
  • Humans
  • Lung Neoplasms (drug therapy, enzymology)
  • Microtubule-Associated Proteins (metabolism)
  • Phosphatidylinositol 3-Kinases (metabolism)
  • Plant Extracts (pharmacology)
  • Proto-Oncogene Proteins c-akt (metabolism)
  • Saponins (pharmacology)
  • Signal Transduction (drug effects)
  • Spirostans (pharmacology)
  • Vacuoles (drug effects)

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