Abstract
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.
Highlights
Dioscoreanone (DN) isolated from Dioscorea membranacea Pierre has been reported to exert potent cytotoxic effects against particular types of cancer
The antiproliferative and cytotoxic effects of DN in several lung cancer cell lines In this study, we further evaluated the antiproliferative effect of DN in two major types of human lung tumorderived cell lines versus the human lung fibroblast cell line MRC-5
At high concentrations of DN, the representatives of each subtype of non-small cell lung cancer (NSCLC) − A549, COR-L23 and NCI-H226 cell lines showed the negative values of cell survival presented as LC50, indicating a net loss of cancer cells
Summary
Dioscoreanone (DN) isolated from Dioscorea membranacea Pierre has been reported to exert potent cytotoxic effects against particular types of cancer. Exploring the precise molecular mechanisms involved in actions of anticancer agents has become an important approach for anticancer drug evaluation and development Among these molecular mechanisms, apoptosis is a highly regulated process of cell death that serves to eliminate heavily damaged cells without injuring surrounding healthy cells, and its dysregulation underlies numerous pathological conditions including cancer [5]. Recent clinical data have revealed that anticancer drugs that restore deregulated apoptosis or apoptosisrelated signaling pathways in cancer cells can significantly improve patient survival for patients who have contracted various advanced cancer diseases [7]. In this context, several plant compounds have been proven, in a more specific manner, to possess promising anticancer activity through their apoptosis-inducing effects [8]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
