Abstract 4801: 2’-Hydroxyflavanone, a diet-derived citrus bioflavonoid, inhibits in vitro and in vivo growth of breast cancer cells by targeting RLIP

Abstract

Abstract Breast cancer remains one of the major causes of cancer deaths in women. Consumption of citrus-fruits is associated with reduced incidence of breast cancer, the most common cancer diagnosed in women across the globe. In this study, we investigated the anticancer potential of 2-Hydroxyflavanone (2HF) in breast cancer. 2HF, a citrus-bioflavonoid, has demonstrated anticancer properties in various cancers, but its anticancer role in breast cancer has not been well studied. We investigated the in-vitro and in-vivo growth inhibitory effects of 2HF in an array of BC lines and in xenograft mouse models of ER-positive and HER2-positive breast cancer cells. Compared to control, 2HF treatment reduced cell viability of breast cancer cells, while, no growth inhibitory effects were observed in non-tumorigenic breast epithelial cells. Further, 2HF inhibited the expression of RLIP, a stress-defensive and anti-apoptotic protein, which is over-expressed in breast cancer cells and simultaneously reduced proliferation of breast cancer cells. Nude mice bearing MCF7 or SKBR3 breast cancer cells xenografts treated with either 2HF or targeting RLIP by RLIP-antisense or RLIP-antibody treatment had significantly lower tumor-weight as compared to corresponding controls. In addition, Western-blotting and immunohistochemical analysis of tumor tissue from control and treatment group mice showed that 2HF decreased protein expression levels of RLIP, and the decrease was similar to those seen following RLIP-antisense treatment. Furthermore, 2HF decreased expression of Ki67, CD31, vimentin, inhibited phosphorylation of AKT and expression of survivin and Bcl2, and increased levels of Bax, E-cadherin, and cleaved-PARP. Therefore, our results indicate that 2HF may suppress breast cancer growth in-vitro and in-vivo by targeting RLIP, and may serve as a potential adjuvant treatment in breast cancer patients. (This work was supported in part by the Department of Defense grant W81XWH-16-1-0641. Funding from the Beckman Research Institute of City of Hope is also acknowledged). Citation Format: Sharad S. Singhal, Shireen Chikara, Jyotsana Singhal, David Horne, Ravi Salgia, Sanjay Awasthi. 2’-Hydroxyflavanone, a diet-derived citrus bioflavonoid, inhibits in vitro and in vivo growth of breast cancer cells by targeting RLIP [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4801.