1. β-Elemene induces apoptosis in human renal-cell carcinoma 786-0 cells through inhibition of MAPK/ERK and PI3K/Akt/ mTOR signalling pathways.
- Author
-
Zhan YH, Liu J, Qu XJ, Hou KZ, Wang KF, Liu YP, and Wu B
- Subjects
- Adenine analogs & derivatives, Adenine pharmacology, Carcinoma, Renal Cell pathology, Cell Line, Tumor, Cell Survival drug effects, Chloroquine pharmacology, Extracellular Signal-Regulated MAP Kinases antagonists & inhibitors, Extracellular Signal-Regulated MAP Kinases metabolism, Humans, Kidney Neoplasms metabolism, Kidney Neoplasms pathology, Phosphatidylinositol 3-Kinases metabolism, Phosphoinositide-3 Kinase Inhibitors, Proto-Oncogene Proteins c-akt antagonists & inhibitors, Proto-Oncogene Proteins c-akt metabolism, TOR Serine-Threonine Kinases antagonists & inhibitors, TOR Serine-Threonine Kinases metabolism, Apoptosis drug effects, Carcinoma, Renal Cell drug therapy, Carcinoma, Renal Cell metabolism, Kidney Neoplasms drug therapy, MAP Kinase Signaling System drug effects, Sesquiterpenes pharmacology
- Abstract
Background: Renal-cell carcinoma (RCC) is resistant to almost all chemotherapeutics and radiation therapy. β-Elemene, a promising anticancer drug extracted from a traditional Chinese medicine, has been shown to be effective against various tumors. In the present study, anti-tumor effects on RCC cells and the involved mechanisms were investigated., Methods: Human RCC 786-0 cells were treated with different concentrations of β-elemene, and cell viability and apoptosis were measured by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay and flow cytometry, respectively. Protein expression was assayed by western blotting. Autophagy was evaluated by transmission electron microscopy., Results: β-Elemene inhibited the viability of 786-0 cells in a dose- and time-dependent manner. The anti-tumor effect was associated with induction of apoptosis. Further study showed that β-elemene inhibited the MAPK/ERK as well as PI3K/Akt/mTOR signalling pathways. Moreover, robust autophagy was observed in cells treated with β-elemene. Combined treatment of β-elemene with autophagy inhibitors 3-methyladenine or chlorochine significantly enhanced the anti-tumor effects., Conclusions: Our data provide first evidence that β-elemene can inhibit the proliferation of RCC 786- 0 cells by inducing apoptosis as well as protective autophagy. The anti-tumor effect was associated with the inhibition of MAPK/ERK and PI3K/Akt/mTOR signalling pathway. Inhibition of autophagy might be a useful way to enhance the anti-tumor effect of β -elemene on 786-0 cells.
- Published
- 2012
- Full Text
- View/download PDF