The antitumour effects of eudesmin on lung cancer by inducing apoptosis via mitochondria-mediated pathway in the tumour cells

Abstract

Context: Limonoids possess broad range of biological activities, including antitumour, antimicrobial and antioxidant activities, etc. Eudesmin (EDN) is a type of limonoid which also possesses various activities. However, there is no report on the antitumour lung cancer (LC) activities of this compound. Objective: The present study investigates the antitumour effects of EDN and its potential molecular mechanisms. Materials and methods: The in vitro antitumour effects of EDN on LC A549 cells were evaluated by using MTT assay. The in vivo antitumour effects were investigated on a xenograft athymic nude mouse model. The mice were administered orally with EDN (10, 20 and 40 mg/kg) once daily for 28 days. Effects of EDN on apoptosis-related or signalling proteins (Bcl-2, Bax, caspase-3, caspase-9, P53, Akt and JNK) were assayed by western blot analysis. Results: EDN showed significant inhibitory effects on the growth of LC A549 cells in vitro with the half maximal inhibitory concentration (IC50) of 18.3 μM. By treating with EDN (10, 20 and 40 μM), expression of caspase-3, caspase-9, Bax, P53 and phosphorylated JNK in A549 cells were significantly upregulated, whereas expression of Bcl-2 and Akt phosphorylation were significantly down-regulated. Interestingly, EDN-induced apoptosis could be attenuated by JNK inhibitor. In addition, in vivo experiments also indicated EDN (10, 20 and 40 mg/kg) had significant antitumour effects (p < 0.01) on nude mice. Conclusions: Overall, the results indicated that EDN possesses significant antitumour effects on LC and the possible mechanism might be related to induction of mitochondria-mediated apoptosis.

Keywords

• a549 cells
• akt/jnk signalling pathway
• molecular mechanisms