Growth arrest and apoptosis via caspase activation of dioscoreanone in human non-small-cell lung cancer A549 cells

BMC Complementary and Alternative Medicine

Research Article

Arunporn Itharat¹  Pintusorn Hansakul²  Kalaya Aree³  Sermkiat Tanuchit⁴ 

[1] Department of Applied Thai Traditional Medicine Center, Faculty of Medicine, Thammasat University, Rangsit Campus, 12120, Khlong Luang, Pathum Thani, Thailand;Division of Biochemistry, Department of Preclinical Science, Faculty of Medicine, Thammasat University, Rangsit Campus, 12120, Khlong Luang, Pathum Thani, Thailand;Division of Microbiology, Department of Preclinical Science, Faculty of Medicine, Thammasat University, Rangsit Campus, 12120, Khlong Luang, Pathum Thani, Thailand;Research Administration Office, Faculty of Medicine, Thammasat University, Rangsit Campus, 12120, Khlong Luang, Pathum Thani, Thailand;

关键词: Dioscoreanone;    Dioscorea membranacea;    Antiproliferative;    Apoptosis;    Caspase activation;   

DOI  :  10.1186/1472-6882-14-413

 received in 2014-01-06, accepted in 2014-10-16,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundDioscoreanone (DN) isolated from Dioscorea membranacea Pierre has been reported to exert potent cytotoxic effects against particular types of cancer. The present study was carried out to investigate the cytotoxicity of DN against a panel of different human lung cancer cell lines. The study further examined the underlying mechanisms of its anticancer activity in the human lung adenocarcinoma cell line A549.MethodsAntiproliferative effects of DN were determined by SRB and CFSE assays. The effect of DN on cell cycle distribution was assessed by flow cytometric analysis. Apoptotic effects of DN were determined by sub-G1 quantitation and Annexin V-FITC/PI flow cytometric analyses, as well as by changes in caspase-3 activity and relative levels of Bax and Bcl-2 mRNA.ResultsDN exerted antiproliferative and cytotoxic effects on all three subtypes of non-small cell lung cancer (NSCLC) cells, but not on small cell lung cancer (SCLC) cells and normal lung fibroblasts. DN slowed down the cell division and arrested the cell cycle at the G2/M phase in treated A549 cells, leading to a dose- and time- dependent increase of the sub-G1 population (apoptotic cells). Consistently, early apoptotic cells (AnnexinV +/PI-) were detected in those cells that were treated for 24 h and increased progressively over time. Moreover, the highest activity of caspase-3 in DN-treated A549 cells was detected within the first 24 h, and pretreatment with the general caspase inhibitor z-VAD-fmk completely abolished such activity and also DN-induced apoptosis in a dose-dependent manner. Additionally, DN increased the Bax/Bcl-2 ratio in treated A549 cells with time, indicating its induction of apoptosis via the mitochondrial pathway.ConclusionsThis study reveals for the first time that the anticancer activity of DN was induced through regulation of the Bcl-2 family protein-mediated mitochondrial pathway and the subsequent caspase-3 activation in A549 cancer cells, thus supporting its potential role as a natural apoptosis-inducing agent for NSCLC.

【 授权许可】

CC BY   
© Hansakul et al.; licensee BioMed Central Ltd. 2014