The antitumour effects of eudesmin on lung cancer by inducing apoptosis via mitochondria-mediated pathway in the tumour cells. (1st January 2017)

• Record Type: Journal Article
• Authors: Jiang, Li-Li; Sun, Bai-Rong; Zheng, Chao; Yang, Gui-Lun
• Is Part Of: Pharmaceutical biology. Volume 55:Number 1(2017)
• Page Start: 2259
• Page End: 2263
• Publication Date: 2017-01-01
• Subjects: A549 cells -- Akt/JNK signalling pathway -- molecular mechanisms; Pharmacognosy -- Periodicals; Materia medica, Vegetable -- Periodicals; 615.321
• DOI: 10.1080/13880209.2017.1401647
• Languages: English
• ISSNs: 1388-0209

Abstract

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.