Abstract 3801: Role of microRNAs in resveratrol induced breast cancer cell death

Abstract

Abstract Purpose: Breast cancer is the second most common type of cancer in women and several drugs are currently being used against this disease. In spite of the availability of promising chemotherapeutic drugs, it is often observed that tumor cells develop resistance to these drugs rendering them ineffective after prolonged use. Identifying alternative and effective treatment options is thus crucial to improve the life expectancy of breast cancer patients. Resveratrol, a dietary agent is being considered as a potential drug candidate due to its pro-apoptotic properties against cancer cells. Additionally, recently microRNAs (miRNAs), which are small non-coding single stranded RNA molecules, are gaining ground as novel cancer therapeutics due to their capability to alter cell functions including apoptosis. The current study aims to elucidate resveratrol-induced apoptosis in breast cancer cells and to investigate if the effects are mediated via tumor-suppressor miRNAs that negatively regulates anti-apoptotic proteins responsible for development and progression of breast cancer. Objective: The overall objective of this study is to elucidate whether resveratrol-induced apoptosis in breast cancer cells (MCF-7 and MDA-MB-231) is mediated via tumor-suppressor miRNAs. Experimental setup: Cell viability was tested using the cell titer glo assay followed by evaluation of apoptosis induction by Hoechst staining. Western blotting was employed to confirm caspase activation. miRNA expression changes in cells treated with resveratrol was confirmed using a miScript miRNA profiling kit. The role of selected miRNAs was further investigated by transfection experiments using miRNA mimic and inhibitor and Western blotting. Results: Resveratrol induced a dose dependent effect on cell viability and induced apoptosis in treated breast cancer cells. MiRNA data analysis revealed several miRNAs to be regulated in breast cancer cells. MiRNAs hsa-miR-542-3p and hsa-miR-122-5p were the most down-regulated and up-regulated in MCF-7 and MDA-MB-231 cells respectively. Transfection experiments confirmed that the observed effects of resveratrol might be mediated by tumor suppressive miRNAs identified. Conclusion: Resveratrol induces apoptosis in breast cancer cells and this effect is mediated through regulation of key tumor suppressive miRNAs. The conclusions drawn from the study highlights the importance of resveratrol in conjunction with miRNAs as a good therapeutic alternative to induce tumor suppression. Citation Format: Rajkumar Venkatadri, Clayton Wright, Vivek Kaushik, Yogesh Kulkarni, Juan Sebastian Yakisich, Anand Krishnan V. Iyer, Neelam Azad. Role of microRNAs in resveratrol induced breast cancer cell death. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3801. doi:10.1158/1538-7445.AM2015-3801