Abstract LB-167: A novel metabolite of citrus tangeretin epigenetically inhibits the growth of human prostate cancer cells

Abstract

Abstract Prostate cancer is the second leading cause of cancer death in men in the United States. Polymethoxyflavonoids (PMFs) such as tangeretin which exclusively exist in citrus fruit peels have been studied to have many bioactivities. In this study, we investigated the inhibitory effect of the metabolites of tangeretin in human prostate cancer LNCaP and PC3 cells. The results showed that PMF1 is a synthetic tangereitin metabolite can significantly inhibits the growth of LNCaP and PC-3 cells (IC50 14.0 and 13.5 µM, respectively) while PMF1 at 15 µM cannot affect the growth of human normal prostate epithelial RWPE-1 cells. The results of the anchorage-independent growth analysis indicated that PMF1 can suppress the colony formation in LNCaP and PC-3 cells as well as LNCaP and PC-3 stem-like cells which were isolated when the parent cells were cultured in the serum-free medium on the ultra-low attached dishes. Furthermore, PMF1 can induce apoptosis in LNCaP cells in which PMF1 increases protein expressions of Bax and Bad and decreases protein expressions of procaspases-3 and Bcl-2. We also found that PMF1 also decreases the protein levels of DNA Methyltransferase 1 and histone deacetylases 1, 2, and 4/5/9. These results suggested that PMF1 might effectively inhibit the growth of human prostate cancer cells as well as prostate cancer stem cells, which provides new insights in the prevention and treatment of prostate cancer. Citation Format: Yen-Hsiang Chao, Zheng-Yuan Su. A novel metabolite of citrus tangeretin epigenetically inhibits the growth of human prostate cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-167. doi:10.1158/1538-7445.AM2017-LB-167