β-Elemene Induces Apoptosis in Human Renal-cell Carcinoma 786-0 Cells through Inhibition of MAPK/ERK and PI3K/Akt/mTOR Signalling Pathways

Abstract

<b>Background:</b> 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 tobe effective against various tumors. In the present study, anti-tumor effects on RCC cells and the involvedmechanisms were investigated. <br/><b>Methods</b>: Human RCC 786-0 cells were treated with different concentrationsof β-elemene, and cell viability and apoptosis were measured by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and flow cytometry, respectively. Protein expression was assayed by westernblotting. Autophagy was evaluated by transmission electron microscopy. <br/><b>Results</b>: β-Elemene inhibited the viabilityof 786-0 cells in a dose- and time-dependent manner. The anti-tumor effect was associated with induction ofapoptosis. Further study showed that β-elemene inhibited the MAPK/ERK as well as PI3K/Akt/mTOR signallingpathways. Moreover, robust autophagy was observed in cells treated with β-elemene. Combined treatment ofβ-elemene with autophagy inhibitors 3-methyladenine or chlorochine significantly enhanced the anti-tumoreffects. <br/><b>Conclusions</b>: 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 theinhibition of MAPK/ERK and PI3K/Akt/mTOR signalling pathway. Inhibition of autophagy might be a usefulway to enhance the anti-tumor effect of β-elemene on 786-0 cells.