β-Elemene, a novel plant-derived antineoplastic agent, increases cisplatin chemosensitivity of lung tumor cells by triggering apoptosis

Abstract

Abstract. ß-Elemene, a new plant-derived anticancer agent with low toxicity, has been reported to be effective in the treatment of leukemia and solid tumors. In the current study, we explored the therapeutic application of ß-elemene in sensitizing lung cancer cells to cisplatin. ß-Elemene considerably enhanced the inhibitory effect of cisplatin on cell proliferation in a time-and dose-dependent manner in the human non-small cell lung cancer (NSCLC) cell lines H460 and A549. Furthermore, this effect of ß-elemene on cisplatin activity occurred through the induction of apoptosis in NSCLC cells, as assessed by an ELISA-based assay, TUNEL assay and annexin V binding assay. Consistent with these results, the protein levels of Bax and phospho-Bcl-2 increased and those of Bcl-2 and XIAP decreased in cells treated with ß-elemene in combination with cisplatin, compared with the levels in cells treated with either agent alone. Finally, ß-elemene augmented the cisplatin-induced increases in caspase-3, -7, -9 and -10 activities and cleaved caspase-3, -9 and poly(ADP-ribose) polymerase levels in NSCLC cells. These observations suggest that ß-elemene sensitizes NSCLC cells to cisplatin via a mitochondriamediated intrinsic apoptosis pathway involving Bcl-2 family proteins and IAPs (inhibitor of apoptosis proteins). Our data provide a rationale for developing a combination of ß-elemene and cisplatin as a regimen for the treatment of lung carcinoma and other cisplatin-resistant tumors.

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

“…Elemene (1-methyl-1-vinyl-2, 4-diisopropenylcyclohexane) is a novel anticancer agent extracted from the traditional Chinese medicine Rhizoma zedoariae (Li et al, 2009 of China to treat malignant effusions and some solid tumors. This indicates that elemene is a promising agent for the treatment of tumors.…”

Synergistic antitumor effect of β-elemene and etoposide is mediated via induction of cell apoptosis and cell cycle arrest in non-small cell lung carcinoma cells

“…Therefore, new approaches, such as novel drugs with mild toxicities or excellent combination regimens, are needed for the treatment of lung cancer. β-Elemene, a type of anticancer drug with a lower cytotoxicity, has been shown to exhibit anticancer effects in many cancer cells, especially lung cancer cells (12,15). In this study, β-elemene inhibited cell proliferation in a dose-dependent manner in A549 cells.…”

“…In addition, many studies have indicated that the effect of β-elemene on cell death may be mediated via a mitochondrial cytochrome c release-dependent apoptotic pathway and the reduction of Bcl-2 protein expression (11). Some other reports have shown that β-elemene can reverse chemotherapeutic resistance and enhance the radiosensitivity in lung carcinoma and renal transplant carcinoma cells (12,13). Thus, the combination of VP-16 and β-elemene may be a possible treatment for lung cancer.…”

β-elemene Induces Caspase-dependent Apoptosis in Human Glioma Cells in vitro through the Upregulation of Bax and Fas/FasL and Downregulation of Bcl-2

“…It has been reported that beta-elemene arrests chemoresistant ovarian carcinoma at the G2-M phase and inhibits the proliferation of cells (Li et al, 2005). Other reported that β-elemene could induce apoptosis in prostate cancer cells and lung tumor cells (Li et al, 2009;. β-elemene also inhibits the proliferation of HEp-2 laryngeal cancer cells and induces apoptosis in vitro and in vivo.…”