Abstract B60: Enhancing the chemopreventive effect by combining arctigenin and green tea polyphenol with curcumin in prostate and breast cancer cell

The incidence and mortality rates of both prostate and breast cancer are much higher in African-American population compared to other races. Both cancers are typically diagnosed at a later age and subject to dietary factors and obesity. Therefore natural products may be an ideal option for chemoprevention to reduce cancer incidence particularly in the high-risk populations. However, the low bioavailability of most flavonoids limits their application as anti-carcinogenic agents in humans. A novel approach of treatment with a mixture of bioactive compounds in low physiologically achievable concentrations may resolve the limitations of reduced bioavailability. We therefore investigate whether a combination of three natural products arctigenin (Arc), a novel anti-inflammatory lignan from the seeds of Arctium lappa, green tea polyphenol (-)-epigallocatechin gallate (EGCG) and curcumin (Cur) increases the chemopreventive potency at low concentrations of individual compounds. LNCaP prostate cancer cells and MCF-7 breast cancer cells were treated with 2μg/mL Cur, 1μM Arc and 40μM EGCG alone or in combination for 48h. In both cell lines treatment with the mixture of Cur, Arc and EGCG increased the antiproliferative effect by 40% compared to Cur alone. In LNCaP cells both Arc and EGCG increased the pro-apoptotic effect of curcumin. Whereas in MCF-7 cells Arc increased the cell apoptosis of Cur while EGCG enhanced cell cycle arrest at G0/G1 phase. The strongest effects on cell cycle arrest and apoptosis in both cell lines were achieved by combining all three bioactive compounds. The combination treatments significantly increased the ratio of Bax to Bcl-2 proteins, decreased the activation of NFkB, PI3K/Akt and Stat3 pathways and cell migration compared to individual treatments. This study is anticipated to provide a novel, culturally acceptable, and cost-effective regimen to enhance chemoprevention of both prostate and breast cancer particularly in minority populations. Citation Format: Piwen Wang, Bin Wang, Yanyuan Wu, Seyung Chung, Susanne M. Henning, Jaydutt V. Vadgama. Enhancing the chemopreventive effect by combining arctigenin and green tea polyphenol with curcumin in prostate and breast cancer cell. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr B60. doi:10.1158/1538-7755.DISP13-B60