Gupta Rakesh Kumar, Banerjee Ayan, Pathak Suajta, Sharma Chandresh, Singh Neeta
Department of Biochemistry, All India Institute of Medical Science, Ansari Nagar, New Delhi, India.
Asian Pac J Cancer Prev. 2013;14(1):237-42. doi: 10.7314/apjcp.2013.14.1.237.
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.
宫颈癌是女性癌症的第二大常见病因,死亡率很高。顺铂作为一种抗肿瘤药物,通常用于其治疗。然而,顺铂的使用会产生副作用和内在耐药性。海巴戟(诺丽果),一种天然植物产品,已被证明具有抗癌特性。在本研究中,我们使用诺丽果、顺铂以及二者的组合,来研究它们对宫颈癌HeLa和SiHa细胞系的细胞毒性和诱导凋亡作用。我们在此证明,诺丽果/顺铂单独使用及其组合均能够在这两种细胞系中诱导凋亡。与诺丽果相比,顺铂显示出略高的细胞杀伤作用,且它们的组合显示出相加效应。观察到的凋亡似乎尤其通过p53和促凋亡蛋白Bax的上调,以及抗凋亡蛋白Bcl-2、Bcl-XL和生存素的下调来介导。还观察到caspase-9和-3活性增强,表明诺丽果和顺铂在HeLa和SiHa细胞系中均通过凋亡的内在线粒体途径发挥作用。