Abstract 1892: Curcumin suppresses prostate cancer cells through modulation of β-catenin and protein kinase D1

Abstract

Abstract OBJECTIVE: Prostate cancer is the most commonly diagnosed cancer in males in the US. One in every 6th male will be diagnosed with prostate cancer this year. Understanding the molecular basis of prostate cancer progression can serve as a tool for early stage diagnosis and development of novel treatment strategies for this disease. Inappropriate activation of β-catenin signaling is linked to a wide range of cancers, including prostate cancer, resulting in transcription of genes involved in cancer progression such as c-Myc, c-Jun and cyclin D1. However, strategies to regulate this specific signaling pathway are very limited or not well developed. Synthetic or natural products which regulate this signaling pathway can be developed as a novel therapeutic modality for prostate cancer treatment. Curcumin, the active ingredient of turmeric, has shown anti-cancer properties via modulation of a number of different molecular pathways. Herein, we have investigated a putative molecular mechanism involved in curcumin mediated suppression of prostate cancer cell growth and the effect of curcumin on prostate cancer cells growth and its effect on β-catenin transcription activity. MATERIALS AND METHODS: Cellular characteristics of the C4-2 prostate cancer cells were measured using anchorage independent growth, anchorage dependent growth, motility, and proliferation assays. β-catenin/T cell factor (TCF) transcription activity was measured by luciferase reporter assays using reporter constructs Topflash or Fopflash and pRL-TK (Renilla luciferase). The Luciferase activities were assayed using the Dual Glo reagent (dual reporter assay, Promega, Madison, WI). Subcellular localization of Protein Kinase D1 (PKD1) and β-catenin was determined by confocal microscopy. RESULTS: Our results demonstrate that curcumin effectively suppresses prostate cancer cell growth, proliferation and cellular motility. In the luciferase assays, curcumin treatment diminished β-catenin transcription activity in C4-2 prostate cancer cells. Moreover, curcumin treatment influences the translocation of β-catenin from the nucleus to the cell surface membrane. Interestingly, the suppression of β-catenin transcription activity was correlated with the modulation PKD1 expression/phosphorylation within 1-3 hrs post-curcumin treatment. CONCLUSION: These results suggest that curcumin treatment attenuates β-catenin transcription activity in prostate cancer cells via modulating the expression/activation of PKD1. These results suggest a novel molecular mechanism of curcumin related suppression of prostate cancer cell growth. 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 1892.