Kumar Binod, Joshi Jayashree, Kumar Amit, Pandey Badri N, Hazra Banasri, Mishra Kaushala P
Department of Pharmaceutical Technology, Jadavpur University, Raja S.C. Mullick Road, Jadavpur, Calcutta, West Bengal 700032, India.
Mol Cell Biochem. 2007 Oct;304(1-2):287-96. doi: 10.1007/s11010-007-9511-9. Epub 2007 May 30.
The development of radio-resistant tumor cells might be overcome by the use of tumor selective cytotoxic agents in combination with radiation treatment of cancer. Thus, we are exploring the radiomodifying potential of D7, a tumor-inhibitory compound derived from a plant product, diospyrin, in breast carcinoma cells, MCF-7. The present study indicated that D7 could enhance the radiation-induced cytotoxicity and apoptosis through down-regulation of the anti-apoptotic Bcl-2 and COX-2 gene expression, and up-regulation of pro-apoptotic genes, like p53 and p21. The higher expression of PUMA, a pro-apoptotic protein was also observed in the combination treatment. Effect of D7 on up-regulation of p21 expression in irradiated MCF-7 cells was concomitant with the cell cycle arrest in the G1 phase. Thus, it was concluded that D7 could sensitize the effect of radiation in breast carcinoma by regulating the gene expression involved in cell cycle and apoptosis.
通过使用肿瘤选择性细胞毒性药物与癌症放射治疗相结合，可能会克服抗辐射肿瘤细胞的发展。因此，我们正在探索D7的辐射修饰潜力，D7是一种从植物产物柿素衍生而来的肿瘤抑制化合物，作用于乳腺癌细胞MCF-7。本研究表明，D7可通过下调抗凋亡Bcl-2和COX-2基因表达，上调促凋亡基因如p53和p21，增强辐射诱导的细胞毒性和凋亡。在联合治疗中还观察到促凋亡蛋白PUMA的高表达。D7对受照射的MCF-7细胞中p21表达上调的作用与细胞周期停滞在G1期相关。因此，得出结论，D7可通过调节参与细胞周期和凋亡的基因表达，使乳腺癌对辐射作用敏感。
