Curcumin down-regulates neuropilin-1, semaphorin 3a, ccl2 and ccr2 mRNA expression in PC-3 cells

2753 Curcumin is the active phytochemical ingredient of turmeric (Curcuma longa). Turmeric is used frequently as a spice in India and Asia, leading to about 80-200 mg of curcumin ingested daily. The ingestion of high levels of curcumin could be one reason for the lower incidence of prostate cancer (PCa) in these regions compared to the United States. It has been reported that curcumin decreases cell viability and invasion of PCa cell lines; however, the underlying mechanism of curcumin in PCa has not yet been fully elucidated. With this study, we hypothesized that curcumin can regulate the expression of important mediators of proliferation and cell motility in PC-3 cells, a bone-derived metastatic androgen-independent prostate cancer cell line. PC-3 cells were exposed to curcumin (30 μM, 18 hrs), dose and time points that are below the threshold levels at which curcumin decreases cell viability, allowing for a better understanding of the mechanistic effects of curcumin that are separate from any cytotoxic effects. Using inventoried Taqman primers in the 7500 FAST Real-Time PCR system (Applied Biosystems), we found that curcumin suppressed the mRNA expression of important mediators of PCa progression and invasion when compared to an ETOH vehicle control. Curcumin significantly decreased(-68% ± 8% SEM) the expression of neuropilin-1 (NP-1), an important receptor of vascular endothelial growth factor (VEGF) isoform 165 signaling. When highly expressed, NP-1 increases invasion and proliferation of PCa. Curcumin also significantly down-regulated (-74% ± 8% SEM) the mRNA expression of semaphorin 3A, another binding partner of NP-1, which can, depending on various cellular cues, lead to very different yet important changes in cellular invasion and adhesion. Furthermore, we found that curcumin significantly decreased (-86% ± 8.1% SEM) the mRNA expression of chemokine CCL2 (chemokine ligand-2 or monocyte chemotactic protein-1) as well as the small membrane bound G-protein CCL2 receptor, CCR2 (-86% ± 4% SEM). Recent evidence demonstrated that CCL2 is a potent chemoattractant of PC-3 cells and CCR2 levels increase with increased PCa progression. We also observed, using a human CCL2 ELISA kit from Ebiosicences, that PC-3 cells exposed to curcumin, exhibited decreased levels of secreted CCL2 (-61% ± 4% SEM). The effects of curcumin were specific to PC-3 and were not uniformly exhibited when other cell lines (DU145, LNCaP and RWPE1) were studied. These data suggest that exposure of bone-derived PC-3 cells to curcumin results in the suppression of important mediators of PCa progression, and indicate novel mechanisms by which curcumin may decrease PCa growth and metastasis.