Molecular mechanism of ophiopogonin B induced cellular autophagy of human cervical cancer HeLa cells.
- Author:
Qiu-Ju XU
1
;
Li-Li HOU
;
Guo-Qiang HU
;
Song-Qiang XIE
Author Information
1. Institute of Chemical Biology, Henan University, Kaifeng 475004, China.
- Publication Type:Journal Article
- MeSH:
Adenine;
analogs & derivatives;
pharmacology;
Antineoplastic Agents, Phytogenic;
pharmacology;
Apoptosis;
drug effects;
Apoptosis Regulatory Proteins;
metabolism;
Autophagy;
drug effects;
Beclin-1;
Cell Proliferation;
drug effects;
Dose-Response Relationship, Drug;
HeLa Cells;
Humans;
Membrane Proteins;
metabolism;
Microtubule-Associated Proteins;
metabolism;
Ophiopogon;
chemistry;
PTEN Phosphohydrolase;
metabolism;
Phosphorylation;
Plants, Medicinal;
chemistry;
Proto-Oncogene Proteins c-akt;
metabolism;
Ribosomal Protein S6 Kinases, 70-kDa;
metabolism;
Saponins;
pharmacology;
Signal Transduction;
drug effects;
Spirostans;
pharmacology;
TOR Serine-Threonine Kinases;
metabolism;
Up-Regulation
- From:
Acta Pharmaceutica Sinica
2013;48(6):855-859
- CountryChina
- Language:Chinese
-
Abstract:
This study is to investigate the antitumor activity of ophiopogonin B (OP-B). MTT assay, flow cytometric analysis, acridine orange staining, Lyso-Tracker Red staining and HeLa-GFP-LC3 transfect cells assay were used to detect the proliferation activity, apoptosis and autophagy of HeLa cells. The results showed that OP-B exerted potent antiproliferative activity on HeLa cells, the cell growth inhibition effect of OP-B was not due to apoptosis and OP-B could induce autophagy of HeLa cells. OP-B also induced the protein expression up-regulation of Beclin-1 and promoted LC3 I transformation LC3 II, which were representative proteins of autophagy. Furthermore, 3-MA, an inhibitor of autophagy, not only inhibited OP-B-mediated autophagy but also almost completely reversed the antiproliferative effect of OP-B, suggesting that the growth inhibition effect of OP-B was autophagy dependent. Western blotting demonstrated that OP-B inhibited the phosphorylation of Akt and its' downstream vital protein, such as mTOR and p70S6K. In addition, OP-B also induced the protein expression up-regulation of PTEN, which is a negative regulation protein for Akt/mTOR signaling pathway. However, OP-B did not affect the protein expression of total Akt. Collectively, the antitumor effects of OP-B were autophagy-dependent via repression Akt/mTOR signaling pathway. Therefore, OP-B is a prospective inhibitor of Akt/mTOR and may be used as an alternative compound to treat cervical carcinoma.
