title: Induction of mitochondrial-mediated apoptosis by Morinda citrifolia (Noni) in human cervical cancer cells.
abstract: 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 associated with side effects and intrinsic resistance. Morinda citrifolia (Noni), a natural plant product, has been shown to have anti-cancer properties. In this study, we used Noni, cisplatin, and the two in combination to study their cytotoxic 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-apoptotic Bax proteins, as well as down- regulation of the anti-apoptotic Bcl-2, Bcl-XL proteins and survivin. Augmentation in the activity of caspase-9 and -3 was also observed, suggesting the involvement of the intrinsic mitochondrial pathway of apoptosis for both Noni and Cisplatin in HeLa and SiHa cell lines.
authors.affiliation: Department of Biochemistry, All India Institute of Medical Science, Ansari Nagar, New Delhi, India.
authors.forename: Rakesh Kumar
authors.initials: RK
authors.lastname: Gupta
authors.forename: Ayan
authors.initials: A
authors.lastname: Banerjee
authors.forename: Suajta
authors.initials: S
authors.lastname: Pathak
authors.forename: Chandresh
authors.initials: C
authors.lastname: Sharma
authors.forename: Neeta
authors.initials: N
authors.lastname: Singh
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002470:Cell Survival; D002945:Cisplatin / Q000494:pharmacology*; D004357:Drug Synergism; D005260:Female; D006367:HeLa Cells; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D032066:Morinda; D028321:Plant Preparations / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D000077022:Survivin; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000473:pathology*
chemical_list: D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D028321:Plant Preparations; D019253:Proto-Oncogene Proteins c-bcl-2; D000077022:Survivin; D016159:Tumor Suppressor Protein p53; D053148:Caspase 3; D053453:Caspase 9; D002945:Cisplatin