Inflammation has an important role in prostate tumorigenesis. The recruitment of inflammatory monocytes to the tumor site is precipitated by increased levels of the chemo-attractant C-C chemokine ligand 2 (CCL2). In the present study, we test the hypothesis that broccoli-derived cancer protective compounds, indole-3-carbinol (I3C) and 3', 3'-diindolylmethane (DIM), exert anti-inflammatory effects by decreasing CCL2 levels and thereby down regulating CCL2 mediated pathways. Dihydrotestosterone (DHT) induced a time (0-72 hrs) and concentration-dependent (0-1 nM) increase in CCL2 mRNA levels in androgen-responsive LNCaP cells. Consistent with increase in CCL2 mRNA, we also observed increased secretion of CCL2 protein in the media of DHT-treated LNCaP cells. This effect of DHT was mediated through an androgen receptor (AR)-dependent pathway as small inhibitor RNA against AR negated the induction. Conditioned media from androgen-treated cells promoted human monocyte THP-1 cell migration and this effect was blocked by antibody against CCL-2. Both I3C and DIM inhibited promotional effects of DHT on CCL2 expression and monocyte migration in-vitro. These results indicate the effect of I3C and DIM on CCL2 and monocyte migration was androgen dependent. Hence, androgen appeared to stimulate CCL2 secretion and thereby promotes inflammatory micro-environments in prostate tumors. These results suggest that the androgen mediated inflammatory processes are modulated by broccoli-derived compounds.
Citation Format: Thomas Wang, Eun-Kyung Kim, John Milner, Young Kim. Broccoli-derived compounds down regulate C-C chemokine ligand 2 expression and monocyte attraction through androgen-dependent pathway in LNCaP prostate cancer cells. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr A78.