Taraxasterol suppresses the growth of human liver cancer by upregulating Hint1 expression. - GreenMedInfo Summary
Taraxasterol suppresses the growth of human liver cancer by upregulating Hint1 expression.
J Mol Med (Berl). 2018 Jul ;96(7):661-672. Epub 2018 May 27. PMID: 29806073
: Taraxasterol has potent anti-inflammatory and anti-tumor activity. However, the effect and potential mechanisms of Taraxasterol on the growth of human liver cancer have not been clarified. Histidine triad nucleotide-binding protein 1 (Hint1) is a tumor suppressor and its downregulated expression is associated with the development of cancer. Here, we report that Taraxasterol treatment significantly suppressed cell proliferation and induced cell cycle arrest at G0/G1 phase and apoptosis in liver cancer cells, but not in non-tumor hepatocytes. Furthermore, Taraxasterol upregulated Hint1 and Bax, but downregulated Bcl2 and cyclin D1 expression, accompanied by promoting the demethylation in the Hint1 promoter region in liver cancer cells. The effects of Taraxasterol were abrogated by Hint1 silencing and partially mitigated by Bax silencing, Bcl2 or cyclin D1 over-expression in HepG2 cells. Moreover, oral administration with Taraxasterol did not affect body weight, urinary protein levels, and the heart, liver, and kidney morphology in BALB/c mice but effectively inhibited the growth of implanted SK-Hep1 tumor in vivo. Collectively, we demonstrate that Taraxasterol inhibits the growth of liver cancer at least partially by enhancing Hint1 expression to regulate Bax, Bcl2, and cyclin D1 expression. Taraxasterol may be a drug candidate for the treatment of human liver cancer.
KEY MESSAGES: Taraxasterol inhibits growth and induces apoptosis in human liver cancer cells. Taraxasterol enhances Hint1 expression by promoting demethylation in Hint1 promoter. Taraxasterol increases Hint1 levels to regulate Bax, Bcl2, and cyclinD1 expression. The effects of Taraxasterol are abrogated by Hint1 silencing in liver cancer cells. Taraxasterol inhibits the growth of subcutaneously implanted liver cancers in mice.