Garlic-derived compound S-allylmercaptocysteine inhibits hepatocarcinogenesis through targeting LRP6/Wnt pathway
2017
Whether and how garlic-derived S -allylmercaptocysteine (SAMC) inhibits hepatocellular carcinoma (
HCC) is largely unknown. In the current study, the role of low-density lipoprotein receptor (LDLR)-related protein 6 (
LRP6) in
HCCprogression and the anti-
HCCmechanism of SAMC was examined in clinical sample, cell model and xenograft/orthotopic mouse models. We demonstrated that SAMC inhibited cell proliferation and tumorigenesis, while induced apoptosis of human
HCCcells without influencing normal hepatocytes. SAMC directly interacted with Wnt-pathway
co-receptor
LRP6on the cell membrane.
LRP6was frequently over-expressed in the tumor tissue of human
HCCpatients (66.7% of 48 patients) and its over-expression only correlated with the over-expression of β -catenin, but not with age, gender, tumor size, stage and metastasis. Deficiency or over-expression of
LRP6in hepatoma cells could partly mimic or counteract the anti-tumor properties of SAMC, respectively. In vivo administration of SAMC significantly suppressed the growth of Huh-7 xenograft/orthotopic
HCCtumor without causing undesirable side effects. In addition, stable down-regulation of
LRP6in Huh-7 facilitated the anti-
HCCeffects of SAMC. In conclusion,
LRP6can be a potential therapeutic target of
HCC. SAMC is a promising specific anti-tumor agent for treating
HCCsubtypes with Wnt activation at the hepatoma cell surface.
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