Antiproliferative effects of pomegranate extract in MCF-7 breast cancer cells are associated with reduced DNA repair gene expression and induction of double strand breaks

• DOI: 10.1002/mc.21995
• Publication Date: 2013-01-28T09:38:23Z
• Authors: Amit B. Shirode; Prasad Kovvuru; Sridar V. Chittur; Susanne M. Henning; David Heber; Ramune Reliene
• Keywords: Rad50

Pomegranate extract (PE) inhibits the proliferation of breast cancer cells and stimulates apoptosis in MCF-7 cells. While PE is a potent antioxidant, present studies were conducted to examine mechanisms action beyond antioxidation by studying cellular molecular underlying tumorigenesis. inhibited cell growth inducing cycle arrest G2/M followed induction apoptosis. In contrast, antioxidants N-acetylcysteine Trolox did not affect at doses containing equivalent antioxidant capacity as PE, suggesting that inhibition cannot solely be attributed its high potential. DNA microarray analysis revealed downregulated genes associated with mitosis, chromosome organization, RNA processing, replication repair, upregulated involved regulation proliferation. Both quantitative RT-PCR indicated important double strand break (DSB) repair homologous recombination (HR), such MRE11, RAD50, NBS1, RAD51, BRCA1, BRCA2, BRCC3. Downregulation HR correlated increased levels their predicted microRNAs (miRNAs), miR-183 (predicted target RAD50) miR-24 BRCA1), may regulate miRNAs processes. Further, treatment frequency DSBs. These data suggest downregulates which sensitizes DSBs, Because represents novel for therapy, downregulation exploited sensitization tumors anticancer drugs. Copyright © 2013 Wiley Periodicals, Inc.