Parekh Palak, Motiwale Leena, Naik Nishigandha, Rao K V K
Chemical Carcinogenesis Group, Cancer Research Institute, Advanced Centre for Treatment Research and Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai-410208, India.
Exp Toxicol Pathol. 2011 Jan;63(1-2):167-73. doi: 10.1016/j.etp.2009.11.005. Epub 2010 Feb 4.
Resveratrol is a naturally occurring phytoalexin with antioxidant activity. The chemopreventive effects of resveratrol against various types of cancer are well known, though the underlying molecular mechanisms of its action are still not identified. Hepatocellular carcinoma (HCC) is a one of the most lethal malignancies and there is no effective treatment till date. It is known that cyclin D1 is overexpressed in liver cancers. Accordingly we have studied the chemopreventive effects of resveratrol on cyclin D1 expression and the signaling pathways that regulate cyclin D1 in HepG2 cells. Flow cytometry and PCNA western blot data showed that resveratrol inhibits proliferation of HepG2 cells. Also, resveratrol treatment downregulated cyclin D1 as well as p38 MAP kinase, Akt and Pak1 expression and activity in HepG2 cells, suggesting that growth inhibitory activity of resveratrol is associated with the downregulation of cell proliferation and survival pathways. Furthermore, resveratrol treated cells showed increase in ERK activity suggesting possible sensitization to apoptosis. Thus in the present study, we report a three-dimensional relationship between the growth inhibitory effects of resveratrol - decrease in the levels of cyclin D1 - and downregulation of cell proliferation and survival pathways in HepG2 cells leading to cellular degenerative changes. These observations suggest that resveratrol has good potential as effective chemopreventive agent against liver cancer and warrant further studies.
白藜芦醇是一种具有抗氧化活性的天然植物抗毒素。白藜芦醇对各种类型癌症的化学预防作用是众所周知的，但其作用的潜在分子机制仍未明确。肝细胞癌（HCC）是最致命的恶性肿瘤之一，迄今为止尚无有效的治疗方法。已知细胞周期蛋白D1在肝癌中过表达。因此，我们研究了白藜芦醇对HepG2细胞中细胞周期蛋白D1表达以及调节细胞周期蛋白D1的信号通路的化学预防作用。流式细胞术和PCNA免疫印迹数据表明，白藜芦醇可抑制HepG2细胞的增殖。此外，白藜芦醇处理下调了HepG2细胞中细胞周期蛋白D1以及p38丝裂原活化蛋白激酶、Akt和Pak1的表达及活性，这表明白藜芦醇的生长抑制活性与细胞增殖和存活通路的下调有关。此外，经白藜芦醇处理的细胞显示ERK活性增加，提示可能对凋亡敏感。因此，在本研究中，我们报告了白藜芦醇的生长抑制作用、细胞周期蛋白D1水平降低与HepG2细胞中细胞增殖和存活通路下调之间的三维关系，这种关系导致细胞退行性变化。这些观察结果表明，白藜芦醇作为一种有效的肝癌化学预防剂具有良好的潜力，值得进一步研究。
