Abstract 3522: Vitamin D (calcitriol) potentiates CB2-mediated anti-tumor responses in prostate cancer cell lines: Molecular mechanisms and therapeutic potential

Abstract Prostate cancer (PCa) is the most frequently diagnosed non-skin cancer among U.S. men and remains the second leading cause of cancer-related mortality. Vitamin D receptor (VDR) signaling exerts antiproliferative and pro-differentiation effects in prostate tumors, while Cannabinoid Receptor 2 (CB2) has been implicated in immune modulation and antitumor activity. Emerging evidence suggests potential crosstalk between CB2 activation and VDR pathways. We hypothesize that CB2 activation induces VDR expression in prostate cancer cells. DU145 and PC3 cells were plated in complete RPMI for 24 hours, serum-starved for 24 hours, and treated with 10 nM calcitriol, 1 nM AM1241 (CB2 agonist), or starvation media alone. In PC3 cells, AM1241 induced VDR expression at levels comparable to calcitriol, whereas DU145 cells showed minimal induction relative to controls. These preliminary findings suggest a cell line–dependent effect whereby CB2 agonism may enhance VDR expression. Ongoing studies are evaluating whether CB2 activation further augments VDR signaling and modulates its tumor-suppressive functions in prostate cancer. Citation Format: William B. Speed, Cimona Vaughn Hinton, Nakea Pennant, . Vitamin D (calcitriol) potentiates CB2-mediated anti-tumor responses in prostate cancer cell lines: Molecular mechanisms and therapeutic potential abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 3522.