Department of Physiology, Centre for Nanoscience and Nanotechnology, University of Calcutta, 92 APC Road, Kolkata, 700 009, West Bengal, India.
Division Radiation Biology, UGC-DAE CSR Center Kolkata, Bidhan Nagar, Kolkata, 700 098, West Bengal, India.
Sci Rep. 2017 Oct 25;7(1):14043. doi: 10.1038/s41598-017-14211-4.
Failure of treatment for cancer in clinic by radio/chemotherapy is generally attributed to tumour resistance. Therefore, it is important to develop strategies to increase the cytotoxicity of tumour cells by radiation in combination with unique tumour selective cytotoxic agents. We evaluated the potential of ellagic acid (EA) as an enhancer of oxidative stress in cancer cells. HepG2 cells were treated with EA (10 µM) for 12 h prior to exposure of single 7.5 Gy dose of irradiation. Treatment of HepG2 cells with EA and gamma radiation showed increased reactive oxygen species generation, up regulation of p53 protein expression, decreased survival markers level like p-Akt, p-NF-kB and p-STAT3 which were significantly higher after radiation treatment alone. We also found that combination treatment increased G2/M phase cell population, decreased IL-6, COX-2 and TNF-α expression and caused a loss in mitochondrial membrane potential with decreased level of angiogenesis marker MMP-9. Over expression of Bax and activation of caspase 3 indicated the apoptosis of the cells. The results provided a strong unique strategy to kill cancer cells HepG2, using less radiation dose along with effective pro-oxidant dose of EA.
临床上，放射/化学疗法治疗癌症失败通常归因于肿瘤耐药性。因此，开发通过与独特的肿瘤选择性细胞毒性药物联合增强肿瘤细胞辐射细胞毒性的策略非常重要。我们评估了鞣花酸 (EA) 作为增强癌细胞氧化应激的潜力。在暴露于单次 7.5 Gy 剂量的照射之前，将 HepG2 细胞用 EA（10 μM）处理 12 小时。用 EA 和γ射线处理 HepG2 细胞可增加活性氧的产生，上调 p53 蛋白表达，降低存活标志物水平，如单独辐射处理后显著升高的 p-Akt、p-NF-kB 和 p-STAT3。我们还发现联合治疗增加了 G2/M 期细胞群体，降低了 IL-6、COX-2 和 TNF-α 的表达，并导致线粒体膜电位丧失，血管生成标志物 MMP-9 水平降低。Bax 的过表达和 caspase 3 的激活表明细胞凋亡。结果提供了一种强大的独特策略，使用较少的辐射剂量和有效的促氧化剂剂量 EA 来杀死肝癌细胞 HepG2。
