Abstract 2000: Curcumin prevents human prostate cancer cell invasion by inhibiting of matriptase activity

Curcumin has been shown with potent chemopreventive and antitumor effects on prostate cancer. However, the molecular mechanism how curcumin suppresses prostate cancer cell migration and invasion is not well understood. In this study we showed that curcumin could significantly suppress prostate cancer PC3 cell migration and invasion. Moreover, our data also showed that curcumin was able to suppress EGF- or heregulin-stimulated PC-3 cell invasion, as well as androgen-induced LNCaP cell invasion. Curcumin treatment resulted in not only significant reductions on MMP-9 and MMP-2 activities, but also on activated level of matriptase which is a membrane-bound serine protease and has been proposed to play important roles in tumor invasion and malignancy. Matriptase is synthesized as a full length zymogen, which is rapidly stepped into the maturation process, mature form through a cleavage within the SEA domain to from a latent matriptase. Our data further showed that curcumin can inhibit the latent matriptase formation in the maturation process to affect matriptase activity. Furthermore, the reduction of activated matriptase by curcumin was also partly due to curcumin promoting the shedding of activated matriptase into extracellular environment, but not due to curcumin effect on matriptase gene expression. In addition, we established the stable pools of CWR22Rv1 cells with matriptase overexpression and found that expression of matriptase in CWR22Rv1 cells enhanced their invasive ability. With curcumin treatment, the invasive ability induced by matriptase overexpression was significantly suppressed. In summary, the data indicated that curcumin exhibits a suppressive effect on prostate cancer cell invasion, at least in part by down-regulating matriptase activity. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2000. doi:1538-7445.AM2012-2000