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β-Elemene induces apoptosis in human renal-cell carcinoma 786-0 cells through inhibition of MAPK/ERK and PI3K/Akt/ mTOR signalling pathways.
- Source :
-
Asian Pacific journal of cancer prevention : APJCP [Asian Pac J Cancer Prev] 2012; Vol. 13 (6), pp. 2739-44. - Publication Year :
- 2012
-
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.<br />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.<br />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.<br />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.
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 2476-762X
- Volume :
- 13
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Asian Pacific journal of cancer prevention : APJCP
- Publication Type :
- Academic Journal
- Accession number :
- 22938451
- Full Text :
- https://doi.org/10.7314/apjcp.2012.13.6.2739