Derivatives of garlic inhibit prostate cancer cell growth under in vitro and in vivo conditions

Abstract

Despite extensive research worldwide, there is no effective way tocontrol the growth of androgen-independent (AI) prostate cancer.Garlic (Allium sativum) extract has been suggested as an anti-canceragent based on a number of epidemiological studies. As is wellknown several compounds have been isolated from garlic includingthe lipid-soluble allyl sulfur compounds such as diallyl disulfide(DADS) and diallyl trisulfide (DATS) and water soluble compoundssuch as S-allylcysteine (SAC) and S-allylmercaptocysteine (SAMC).We have carried out extensive studies on the effects of SAC andSAMC on prostate cancer cell lines and found that these garlic deriv-atives suppressed prostate cancer cell proliferation, migration andinvasion. This inhibitory effect was associated with induction of mes-enchymal to epithelial transition. More importantly, the SAC andSAMC treatment led to restoration of E-cadherin expression whilethe expression of E-cadherin repressor, Snail, was downregulated.We have also evaluated the effect of these compounds on prostatecancer using a prostate cancer xenograft, CWR22R, and AI prostatecancer in nude mice. The results showed that treatment with thegarlic derivatives inhibited the growth of CWR22R without anydetectable toxic effect on nude mice. The SAC and SAMC inducedgrowth reduction was correlated with a reduction in serum PSA leveland proliferation rate of xenografts. Our results suggest that thesegarlic derivatives may be potential therapeutic agents for the sup-pression of AI prostate cancer.Supported by AICR (05A006-REV2) and RGC grants(HKU7478/03M) to XHW and YCW (HKU7490.03M, 7470/04M,NSFC/RGCN HKU738/03, HKU Foundation Seed Fund, 03).