Radiosensitization by diospyrin diethylether in MCF-7 breast carcinoma cell line.
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.
Kumar
Binod
B
Department of Pharmaceutical Technology, Jadavpur University, Raja S.C. Mullick Road, Jadavpur, Calcutta, West Bengal 700032, India.
Joshi
Jayashree
J
Kumar
Amit
A
Pandey
Badri N
BN
Hazra
Banasri
B
Mishra
Kaushala P
KP
D001943:Breast Neoplasms / Q000532:radiotherapy*; D002277:Carcinoma / Q000532:radiotherapy*; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000235:genetics; D004353:Drug Evaluation, Preclinical; D015972:Gene Expression Regulation, Neoplastic; D019254:Genes, bcl-2; D016158:Genes, p53; D006801:Humans; D008954:Models, Biological; D009285:Naphthoquinones / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D011836:Radiation Tolerance / Q000187:drug effects*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017382:Reactive Oxygen Species / Q000378:metabolism
D009285:Naphthoquinones; D011838:Radiation-Sensitizing Agents; D017382:Reactive Oxygen Species; C526237:diospyrin diethylether; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; C043546:diospyrin