Abstract 4246: Synergistic inhibition of prostate tumor growth and progression by the combination of curcumin and ursolic acid in HiMyc mice

Abstract

Abstract Prostate cancer (PCa) is the second leading cause of cancer death among men in the United States. According to the World Health Organization, approximately one-third of all cancer deaths could be prevented through an increased consumption of natural compounds. Through the use of a two-tiered screening method in PCa cells (depletion of cellular ATP level followed by glutamine uptake) of a phytochemical library, curcumin and ursolic acid were selected for further investigation. Twenty-four hour treatment of LNCaP, 22Rv1 and HMVP2 cells with the combination resulted in significant decreases in expression of members of the miR-17-92 and miR-106b-25 clusters, which are upregulated in PCa and have been shown to be involved in tumorigenesis, cell survival, and metastasis. In the HiMyc mouse model, where mice spontaneously develop primary PCa, supplementing diets with the combination of curcumin (1%) and ursolic acid (0.2%) resulted in significant inhibition of tumor growth and progression compared to diets containing either compound alone. There were no differences in body weight or food consumption in any of the diet groups during the tumor experiment. The current data suggests that the combination of curcumin and ursolic acid synergistically inhibits PCa growth and progression in HiMyc mice, which may be in part due to their effects on microRNA expression. Ongoing studies are further examining the role of specific miRNAs as well as oncogenic signaling pathways potentially involved in the mechanism of synergistic chemopreventive action of this combination. The current data suggest that this novel combination could be a valuable therapeutic option for prevention and/or treatment of PCa. Funding: This work was supported by NIH Grant CA228404. Citation Format: Chelsea A. Friedman, Achinto Saha, John DiGiovanni. Synergistic inhibition of prostate tumor growth and progression by the combination of curcumin and ursolic acid in HiMyc mice. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4246.