Abstract 5672: A novel anti-cancer effect of hesperidin: reversion of epithelial mesenchymal transition in human prostate cancer cells

Abstract

Abstract Prostate cancer is the most common noncutaneous malignancy in men. About one third of prostate cancers invade surrounding tissues, and metastasize to distant organs at the time of diagnosis. Once prostate cancer metastasizes to distant organs, the disease is basically not curable. The median survival for men with metastatic prostate cancer is 1 to 3 years. Epithelial mesenchymal transition (EMT) is a process facilitating cancer cell invasion and metastasis. Hesperidin (3′-5,7-trihydroxy-4′-methoxyflavanone 7-rhamnoglucoside) is a flavonoid found abundantly in citrus fruits. It demonstrates anti-inflammatory, anti-oxidative, and anti-proliferative actions in various cancer types. Its effect on EMT of prostate cancer is not known. We therefore hypothesize that hesperidin inhibits the cell growth and EMT of prostate cancer cells. In our study, we use androgen-sensitive prostate cancer LNCaP cells, androgen-insensitive Du 145 and PC3 cells, and benign prostate BPH-1 cells. These cell lines are treated with increasing concentrations of hesperidin, from 10 µM to 200 µM. We first examine the effects of hesperidin on cell viability by MTT assays. Hesperidin inhibits all three prostate cancer cell viability in a dose dependent manner but it has no significant effects on that of normal prostate cells, BPH-1. We then examine whether hesperidin reverses EMT in these cells by investigating the migration ability and the expression of EMT marker. Hesperidin at 100 µM and 200 µM inhibits the cell migration ability of PC3 and LNCaP as showed by wound scratch assay. Next, we examine expression of E-cadherin, a molecular marker for EMT, by immunohistochemistry. Hesperidin at 100 µM significantly enhances the membranous expression of E-cadherin in LNCaP cells after 48 hours of treatment as compared to the control. There are no significant changes in androgen receptor (AR) protein level or PSA mRNA after hesperidin treatment suggestive that the effects of hesperidin on LNCaP cells are AR-independent. In conclusions, our data provide novel findings that hesperidin can induce the reversion of EMT in prostate cancer cells. Hesperidin may therefore be a potential chemopreventive agent in human prostate cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5672.