Ellagic Acid Enhances Apoptotic Sensitivity of Breast Cancer Cells to γ-Radiation

ABSTRACT

Herbal polyphenols have gained increased significance because of the promises they hold in the prevention and treatment of cancer. There exists an enormous opportunity for the screening and valuation of natural dietary compounds in the development of an effective chemopreventive drug and radiosensitizer that may be of practical use for patients undergoing cancer therapy. This study describes the effect of the flavonoid ellagic acid (EA) on gamma-irradiated human breast cancer MCF-7 cells in vitro when administered alone or in combination with radiation. It was interesting to find the radioprotective effect of EA on NIH3T3, which is a normal cell line. Irradiation of breast tumor cells in the presence of EA (10 μM) to doses of 2 and 4-Gy gamma radiation produced a marked synergistic tumor cytotoxicity while it was found to aid recovery from the radiation damage to NIH3T3 cells. When cells were given a combined treatment of EA and radiation, the cell death increased to 21.7% and 20.7% in the 2 and 4-Gy-treated cells respectively, significantly (P < 0.05) reducing the capacity of MCF-7 cells to form colonies. Even at 24 h, 38 foci/cell were observed in samples that were given the combined treatment, suggesting the cells' inability in repairing the damage. Also, increased apoptosis in EA+ 2Gy (50%) and EA+ 4 Gy (62%)-treated cells was observed in the the sub-G1 phase of the cell cycle. A 6.2-fold decrease in the mitochondrial membrane potential was observed in the combined treatment of EA and IR that facilitated the upregulation of pro-apopttotic Bax and downregulation of Bcl-2, pushing the MCF-7 cells to undergo an apoptotic cell death. It is suggested that EA may be a potential drug adjuvant for improving cancer radiotherapy by increasing tumor toxicity and reducing the normal cell damage caused by irradiation.

Acknowledgments

We would also like to thank the authorities of Bhabha Atomic Research Centre for permitting the usage of facilities to conduct the above-mentioned work. Our special thanks to Dr. BN Pandey and extended thanks to Prayag Amin, Sanjay Shinde, Hansa Yadav, Manzoor Ali, and Vasumathy for providing technical assistance.

Declaration of Interest

The authors report no conflict of interest. The authors alone are responsible for the content and writing of the paper.

Funding

We thank UGC; Government of India for the grant (201112-RGNFSC-MAH-114) of Rajiv Gandhi Senior Research Fellowship to Ms. Vidhula Ahire.