Abstract 3702: 2-Hydroxyflavanone inhibits renal cancer growth by inhibiting tumor cell proliferation and angiogenesis

Abstract

Abstract Renal cell carcinoma (RCC) is one of the top ten cancers prevalent in USA. Loss-of-function mutation in the VHL is an established risk factor for RCC contributing to 75% of total reported cases of RCC. Loss of VHL leads to highly vascularized phenotype of renal tumors. Intake of oranges has been proven to reduce the risk of RCC in multi-center international clinical trials. Hence, we studied effects of 2HF, an active anti-cancer compound of oranges, in VHL- mutant RCC. Our in vitro investigations revealed that 2HF selectively inhibits VHL-mutant RCC by inhibiting EGFR signaling which is increased due to VHL mutations in RCC. Our results also revealed for the first time, that 2HF inhibits GSTπ activity. 2HF inhibited cyclin B1 and CDK4, and induced G2/M phase arrest in VHL-mutant RCC. Importantly, 2HF inhibited the angiogenesis in VHL-mutant RCC by decreasing VEGF expression. Our in vivo studies in mice xenografts confirmed our in vitro results as evident by decreased levels of proliferation marker, Ki67 and angiogenic marker CD31, in 2HF treated (0.01%, w/w) mice xenografts of VHL-mutant RCC. 2HF also increased the expression of E-cadherin in VHL-mutant RCC which would be of significance in restoring the normal epithelial phenotype. Collectively, our in vitro and in vivo results revealed the potent anti-proliferative and anti-angiogenic effects of 2HF in VHL-mutant RCC, sparing normal cells, which could have significant implications not only in the specific management of VHL-mutant RCC but also in treating other VHL syndromes with highly vascularized phenotype. (Supported in part by NIH grant CA 77495 (SA), CA 155350, Cancer Research Foundation of North Texas, and Institute for Cancer Research & the Joe & Jessie Crump Fund for Medical Education (SSS)) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3702. doi:10.1158/1538-7445.AM2011-3702