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

Department of Biochemistry, All India Institute of Medical Science, Ansari Nagar, New Delhi, India E-mail : .
Asian Pacific journal of cancer prevention: APJCP (Impact Factor: 2.51). 01/2013; 14(1):237-242. DOI: 10.7314/APJCP.2013.14.1.237
Source: PubMed


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.

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Available from: Chandresh Sharma, May 04, 2015
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    • "In fact, Noni acted as an in-vitro antigenotoxic agent (Thitiorul et al., 2008) but not anticlastogenic (Ratanavalachai, Thitiorul, & Nandhasri, 2008a, 2008b). As an antitumor agent (Li et al., 2013), which induced apoptosis in some in-vitro researches (Kharis, Hawariah, & Normah, 2009; Kharis, Hawariah, & Normah, Aishah, 2010; Gupta, Banerjee, Pathak, Sharma, & Singh, 2013), Noni powder (750 mg/kg body weight/day) showed no significant change in apoptosis in the lymph nodes, spleens and lungs of experimental animals (Al-Nuaimee, Hazilawati, Jasni, Noordin, & Rosly, 2012). "
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    ABSTRACT: Morinda citrifolia L., “Noni”, has been used as a food and traditional medicine in Polynesian culture. Noni is now widely available in the global market, mainly as juices and dietary supplements. Here, we review recent research on Noni and its products. We summarize research on the beneficial therapeutic and nutritional properties of Noni, as well as that on the effects of post-harvest storage and processing methods on the properties of Noni products. The aim of this review is to provide a comprehensive data on the technical and nutritional advances related to Noni fruit, including those described in recent patents.
    Trends in Food Science & Technology 11/2014; DOI:10.1016/j.tifs.2015.06.004 · 4.65 Impact Factor
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    • "These cell lines were chosen for the study because they harbor the human papilloma virus (HPV) type 18 (HeLa) and type 16 (SiHa) genotypes. These HPVs have been shown in multi-institutional studies as etiological agents in the development of cervical cancer and these genotypes account for >70% of all HPV DNA positive invasive cervical cancers (Gupta et al., 2013). "
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    ABSTRACT: Background: Cervical cancer, the second most common cancer in women, 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 antioxidant activities in vitro and in vivo. Materials and methods: Both HeLa and SiHa cervical cancer cell lines were treated with 10% Noni, 10 mg/dl cisplatin, or a combination of both 10% Noni and 10 mg/dl cisplatin for 24 hours. Post culturing, the cells were pelleted and stored at -70oC for malondialdehyde and catalase assays. Results: On treatment with Noni, CP, and their combination, the level of MDA decreased by 0.76 fold, 0.49 fold, and 0.68 fold respectively in HeLa cells; and by 0.93 fold, 0.67 fold, and 0.79 fold respectively in SiHa cells, as compared to their controls; whereas catalase activity increased by 1.61 fold, 0.54 fold, and 2.35 fold, respectively in HeLa cells; and by 0.98 fold, 0.39 fold, and 1.85 fold respectively in SiHa cells. Conclusions: A decrease in level of lipid peroxidation and an increase in catalase activity were observed with Noni by itself and the effect ameliorated changes observed with cisplatin when given in combination.
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    ABSTRACT: Cervical cancer is a major health problem worldwide and is the most frequent cause of cancer in women in India. Early detection and affordable drugs with clinical efficacy have to go hand-in-hand in order to comprehensibly address this serious health challenge. Plant-based drugs with potent anticancer effects should add to the efforts to find a cheap drug with limited clinical side effects. Keeping this very purpose in mind, an attempt has been made in this review to explore the potential of plant extracts or constituents known to exhibit antitumorigenic activity or exert cytotoxic effect in human cervical carcinoma cells. Alkaloids such as those isolated from C. vincetoxicum and T. Tanakae, naucleaorals A and B, isolated from the roots of N. orientalis, (6aR)-normecambroline, isolated from the bark of N. dealbata appear promising in different human cervical carcinoma cells with the IC50 of 4.0-8 μg/mL. However, other compounds such as rhinacanthone and neolignans isolated from different plants are not far behind and kill cervical cancer cells at a very low concentrations. Among plant extracts or its constituents that enhance the effect of known anticancer drugs, noni, derived from the plant M. citrifolia perhaps is the best candidate. The cytotoxic potency and apoptotic index of cisplatin was found to significantly enhanced in combination with noni in different human cervical carcinoma cells and it therefore holds significance as promising herbal-based anticancer agent. However, efficacy needs to be further investigated in various cervical cell lines and more importantly, in in vivo cervical cancer models for possible use as an alternative and safe anticancer drug.
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