Title

 

Authors

A. Angelucci, Pa. Sanità, P. Muzi, M. Bologna

Dpt of Experimental Medicine, University of L’Aquila, 67100 L’Aquila

 

Abstract

Curcumin (diferuloylmethane), the major yellow pigment from the rhizomes of turmeric (Curcuma longa Linn), has anticancer properties. We and other authors have previously reported that arachidonic acid (AA) metabolites generated by both 5-lipoxygenase (5-LOX) and cyclooxygenase-2 (COX-2) are potent mitogenic factors for prostate carcinoma (PCa) cells. While 5-LOX controls cell survival through the regulation of the Bcl-2/Bax ratio, COX-2 activity stimulates the release of transforming growth factor-alpha (TGF-alpha) and pro-inflammatory cytokines. We demonstrated that curcumin blocked IkBalpha phosphorylation and degradation, leading to abrogation of NFkappaB activation and thus regulating the expression of COX-2. Thus, the presence of curcumin in culture medium was sufficient to repress in PCa cells AA-induced gene transcription of autocrine and paracrine growth factors. In particular the inhibition of TGF-alpha resulted in a significant reduction in clonal growth and migration of PCa cells. Moreover repression of tumour necrosis factor and interleukin-1 beta by curcumin in AA-primed PCa cells resulted particularly effective in reducing  the tumor-associated aberrant response in bone marrow stromal cells. This aspect is mostly important because PCa cells are able to form metastasis in bone medulla.  Overall, our results indicate that curcumin mediates in PCa cells its antiproliferative and antimetastatic effects through inhibition of AA signaling pathways. Because its safety profile, curcumin activity against PCa should be further investigated.