Abstract A78: Broccoli-derived compounds down regulate C-C chemokine ligand 2 expression and monocyte attraction through androgen-dependent pathway in LNCaP prostate cancer cells

Abstract

Abstract 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.