Radiosensitization by diospyrin diethylether in MCF-7 breast carcinoma cell line Binod Kumar Æ Jayashree Joshi Æ Amit Kumar Æ Badri N. Pandey Æ Banasri Hazra Æ Kaushala P. Mishra Received: 31 December 2006 / Accepted: 7 May 2007 / Published online: 30 May 2007 Ó Springer Science+Business Media B.V. 2007 Abstract 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-in- duced 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. Keywords Quinonoids Á Diospyrin Á Radiation Á Apoptosis Á p53 Á Bcl-2 Introduction Cancer is a multifactorial disease that, in many cases, requires multimodal treatment involving combination of conventional chemo- and radiotherapy regimens. The sig- naling pathways that account for the efficacy of these treatments have become increasingly clear in recent years [1]. This knowledge has facilitated the clinical study of numerous biological modifiers that might increase the potency of treatment and reduce undesirable side effects through enhancement of radiosensitivity of tumor cells, thereby helping to optimize the radiation dose aimed at strategic improvement of the therapeutic outcome. Hence, a tumor selective cytotoxic agent might be used to regulate some gene products, and increase the sensitivity of cancer cells to apoptotic induction. In this way it might be possible to overcome the development of radioresistance, which involves anti-apoptotic signal transduction pathways and markedly impairs the efficacy of tumor radiotherapy [2]. The radiosensitizing property of these agents could often be correlated with their ability to inhibit well-studied molecular targets [3]. Recently, several medicinal plant products and their derivatives have gained attention for their ability to modulate a number of signaling pathways involved in the initiation and progression of cancer [4–7]. Thus, understanding the potential chemopreventive mech- anisms of naturally occurring compounds would be a key to the future application of such agents for human health. For example, curcumin, a plant-derived polyphenol, con- fers radiosensitizing effect in human prostate cancer cell line PC-3 cells by down-regulating radiation-induced pro- survival factors [8]. Currently, breast cancer, a solid neoplasm, is the most frequent cancer type among women, causing more than 5 lakh deaths per year worldwide [9]. Since radiotherapy is one of the major options in the management of breast cancer, the application of plant-derived anti-tumor com- pounds in combination with ionizing radiation (IR) has generated considerable attention in recent times [10, 11]. B. Kumar Á B. Hazra (&) Department of Pharmaceutical Technology, Jadavpur University, Raja S.C. Mullick Road, Jadavpur, Calcutta, West Bengal 700032, India e-mail: hazra1@vsnl.com; banasrihazra@yahoo.co.in J. Joshi Á A. Kumar Á B. N. Pandey Á K. P. Mishra Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai 400 085, India 123 Mol Cell Biochem (2007) 304:287–296 DOI 10.1007/s11010-007-9511-9