diospyrin and Breast-Neoplasms

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.

Topics: Breast Neoplasms; Carcinoma; Cell Cycle; Cell Line, Tumor; Cyclooxygenase 2; Drug Evaluation, Preclinical; Gene Expression Regulation, Neoplastic; Genes, bcl-2; Genes, p53; Humans; Models, Biological; Naphthoquinones; Radiation Tolerance; Radiation-Sensitizing Agents; Reactive Oxygen Species