Induction of Mitochondrial-Mediated Apoptosis by Morinda Citrifolia (Noni) in Human Cervical Cancer Cells

Cervical cancer is the second most common cause of cancer in women and has a high mortality rate. Cisplatin,an antitumor agent, is generally used for its treatment. However, the administration of cisplatin is associatedwith side effects and intrinsic resistance. Morinda citrifolia (Noni), a natural plant product, has been shown tohave anti-cancer properties. In this study, we used Noni, cisplatin, and the two in combination to study theircytotoxic and apoptosis-inducing effects in cervical cancer HeLa and SiHa cell lines. We demonstrate here,that Noni/Cisplatin by themselves and their combination were able to induce apoptosis in both these cell lines.Cisplatin showed slightly higher cell killing as compared to Noni and their combination showed additive effects.The observed apoptosis appeared to be mediated particularly through the up-regulation of p53 and pro-apoptoticBax proteins, as well as down- regulation of the anti-apoptotic Bcl-2, Bcl-XL proteins and survivin. Augmentationin the activity of caspase-9 and -3 was also observed, suggesting the involvement of the intrinsic mitochondrialpathway of apoptosis for both Noni and Cisplatin in HeLa and SiHa cell lines.