Garlic-derived S-allylmercaptocysteine is a novel in vivo antimetastatic agent for androgen-independent prostate cancer.
OBJECTIVE
There is epidemiologic evidence that high garlic consumption decreases the incidence of prostate cancer, and compounds isolated from garlic have been shown to have cancer-preventive and tumor-suppressive effects. Recent in vitro studies in our laboratory have shown that garlic-derived organosulfur compound S-allylmercaptocysteine suppresses invasion and cell motility of androgen-independent prostate cancer cells via the up-regulation of cell-adhesion molecule E-cadherin. S-allylmercaptocysteine is therefore a potential antimetastatic drug with broad clinical applications that we tested in vivo for the first time in this study.


METHODS
We used a newly established fluorescent orthotopic androgen-independent prostate cancer mouse model to assess the ability of S-allylmercaptocysteine to inhibit tumor growth and dissemination.


RESULTS
We showed that oral S-allylmercaptocysteine not only inhibited the growth of primary tumors by up to 71% (P < 0.001) but also reduced the number of lung and adrenal metastases by as much as 85.5% (P = 0.001) without causing notable toxicity. This metastatic suppression was accompanied by a 91% reduction of viable circulating tumor cells (P = 0.041), suggesting that S-allylmercaptocysteine prevents dissemination by decreasing tumor cell intravasation.


CONCLUSIONS
Our results provide in vivo evidence supporting the potential use of S-allylmercaptocysteine as an E-cadherin up-regulating antimetastatic agent for the treatment of androgen-independent prostate cancer. This is the first report of the in vivo antimetastatic properties of garlic, which may also apply to other cancer types.
Howard
Edward W
EW
Cancer Biology Group, Department of Anatomy, Faculty of Medicine, University of Hong Kong, Hong Kong.
Ling
Ming-Tat
MT
Chua
Chee Wai
CW
Cheung
Hiu Wing
HW
Wang
Xianghong
X
Wong
Yong Chuan
YC
D000728:Androgens / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D003545:Cysteine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005737:Garlic / Q000737:chemistry*; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D014162:Transfection; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D000728:Androgens; D000970:Antineoplastic Agents; D018931:Antineoplastic Agents, Hormonal; C086300:S-allylmercaptocysteine; D049452:Green Fluorescent Proteins; D003545:Cysteine