1a.Objectives (from AD-416):
The objective of this agreement is to work together to conduct studies examining the effects of phytochemicals on cancer cells and cancer stem cells. Studies will focus on genes important in the process of carcinogenesis.
1b.Approach (from AD-416):
ARS will use cell culture models of prostate cancer cells or prostate cancer stem cells to test the effects of diet-derived phytochemicals on their ability to inhibit carcinogenesis. The focus will be on cellular pathways that may be important in the carcinogenesis process, including steroid hormone-related pathways, xenobiotic metabolism, etc. Gene expression of marker genes for specific pathways will be monitored to assess biological efficacies of various diet-derived components. The Cooperator will provide funding for material and supplies for the experiments as well as funding for personnel. ARS will conduct experiments and provide mentoring of visiting scientists involved in the project.
The signaling lymphocyte activation molecule (SLAM)- family members including CD84 are now recognized as important immuno-modulatory receptors with roles in cytotoxicity, humoral immunity, autoimmunity, cell survival, lymphocyte development, and cell adhesion. We found treatment of human THP-1 monocytic cell with cruciferous vegetable-derived compounds indole-3-carbinol (I3C) or diindolylmethane (DIM) leads to significant inhibition of CD84 mRNA expression. The down regulation of CD84 appeared to correlate with I3C and DIM’s ability to inhibit an inflammation-induced increase in IL-1ß mRNA expression. Other inflammation-induced cytokines were not affected by I3C or DIM. These results suggested I3C or DIM may modulate immune responses through inflammation mediated events.