Antitumor effect of β-elemene in non-small-cell lung cancer cells is mediated via induction of cell cycle arrest and apoptotic cell death

Abstract

Beta-elemene is a novel anticancer drug, which was extracted from the ginger plant. However, the mechanism of action of beta-elemene in non-small-cell lung cancer (NSCLC) remains unknown. Here we show that beta-elemene had differential inhibitory effects on cell growth between NSCLC cell lines and lung fibroblast and bronchial epithelial cell lines. In addition, beta-elemene was found to arrest NSCLC cells at G2-M phase, the arrest being accompanied by decreases in the levels of cyclin B1 and phospho-Cdc2 (Thr-161) and increases in the levels of p27(kip1) and phospho-Cdc2 (Tyr-15). Moreover, beta-elemene reduced the expression of Cdc25C, which dephosphorylates/activates Cdc2, but enhanced the expression of the checkpoint kinase, Chk2, which phosphorylates/ inactivates Cdc25C. These findings suggest that the effect of beta-elemene on G2-M arrest in NSCLC cells is mediated partly by a Chk2-dependent mechanism. We also demonstrate that beta-elemene triggered apoptosis in NSCLC cells. Our results clearly show that beta-elemene induced caspase-3, -7 and -9 activities, decreased Bcl-2 expression, caused cytochrome c release and increased the levels of cleaved caspase-9 and poly(ADP-ribose) polymerase in NSCLC cells. These data indicate that the effect of beta-elemene on lung cancer cell death may be through a mitochondrial release of the cytochrome c-mediated apoptotic pathway.

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

“…Studies indicate that ß-elemene is a broad-spectrum anticancer agent, with efficacy in treating leukemia, brain tumor, breast cancer and liver cancer (13)(14)(15)(16)(17). Recently, ß-elemene has been shown to induce tumor cell apoptosis and cell cycle G2/M arrest, as evidenced by DNA ladder formation, morphological alterations and flow cytometric data; these findings suggest that apoptosis and G2/M arrest triggered by ß-elemene contribute to its inhibition of cell proliferation (13)(14)(15)(16)(17)(18). ß-Elemene has also been shown to decrease the level of Bcl-2, an anti-apoptotic protein (18).…”

Cytotoxic evaluation of essential oil from Zanthoxylum rhoifolium Lam. leaves

“…leaves was determined (Moura et al, 2006). Despite not being preponderant, the oil analyses showed that among its numerous constituents, there are some components described in literature as cytotoxic substances against tumoral cells, such as β-caryophyllene (5.9%), β-elemene (3.1%), δ -elemene (1.6%), α-humulene (2.3%) (Duh et al, 1999;Legault et al, 2003;Sibanda et al, 2004;Sylvestre et al, 2005;Stravi et al, 2005;Tatman and Mo, 2002;Wang et al, 2005;Sylvestre et al, 2006;Hou et al, 2006;Tao et al, 2006;Xiao et al, 2006. Some other components with no or low antitumoral activity were also found in this species, eg sphathulenol (3.8%), á-pinene (6.4%), linalool (0.5%), myrcene (0.6%) (Fullas et al, 1994;Tatman & Mo, 2002;Stavri et al, 2005).…”

Chemical composition and biological activities ofEruca vesicariasubsp. longirostrisessential oils

“…This indicates that elemene is a promising agent for the treatment of tumours. b-Elemene, the major active component of elemene, has been shown to be effective against various tumours such as lung cancer, prostate cancer and glioblastoma (Wang et al 2005;Yao et al 2008;Li et al 2010).…”