Molecular and Cellular Pharmacology, Vol 1, No 4 (2009)

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Enhancement of Gamma Radiation-induced Cytotoxicity of Breast Cancer Cells by Curcumin

Swati Girdhani, Mansoor M. Ahmed, Kaushala P. Mishra

Abstract


Failure of cancer treatment in clinic by radio/chemotherapy is generally attributed to tumor resistance. It is therefore, important to develop strategies to increase cytotoxicity of tumor cells by radiation in combination with new tumor selective cytotoxic agents. Curcuminoids are a group of phenolic compounds isolated from the rhizome of Curcuma longa with various pharmacological properties. They exhibit growth inhibitory effects on a broad range of tumors and have recently been shown to act as potent radiosensitizers. Present work was designed to study the combined effects of curcumin and gamma radiation on breast cancer cells. We used MCF-7 human breast cancer cells that were treated with curcumin prior to gamma irradiation. Cell viability, induction of apoptosis, generation of ROS and loss of mitochondrial membrane potential were determined. Our results indicated that curcumin (5 mM) exposure prior to irradiation decreased survival to 38% as compared to 52% by radiation (5 Gy) alone.  It was found that treatment of cells with curcumin before radiation caused increased induction in apoptotic death as assessed by PI and annexin V dual staining and the appearance of sub G1 peak in PI cell cycle analysis. Interestingly, curcumin treatment of MCF-7 cells lead to a decrease in the generation of intracellular ROS along with a loss of the mitochondrial membrane potential. These findings, therefore, indicate that pre-treatment with curcumin caused significant enhancement of gamma radiation-induced cell death in MCF-7 cells and this effect was potentially mediated via ROS-independent pathway.


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