Chemopreventive and antitumor effects of benzyl isothiocynate on HCC models: A possible role of HGF /pAkt/ STAT3 axis and VEGF

Background: Benzyl isothiocyanate (BITC) is a member of the isothiocyanate compounds that found in cruciferous vegetables. BITC has a potential anticancer effect in different types of tumors. Few studies referred to the antineoplastic effect of BITC against HCC. The mechanism of BITC concerning retardation of HCC progression is incompletely understood. Aim of the work: This study evaluated the role of HGF, pAkt and STAT3 in BITC induced HCC growth retardation. Method: HCC was induced in mice using diethylnitrosamine (DEN) 75 mg/kg once a week for 4 weeks. BITC 10 and 20 mg/kg was given to mice orally each day for 10 weeks. The HCC cell lines HepG2 and Huh-7 were also used to evaluate the effect of BITC on tumor cells behavior. Immunoassay was used to detect expressions of caspase-3 activity, VEGF, MMP-2, TNF-alpha, HGF and pAkt. STAT3 expression was detected in liver tissues using immunohistochemical staining. Results: BITC has a potential role in suppressing hepatic precancerous lesion progression in mice. The drug increased caspase-3 activity in tumor cells and inhibited the angiogenic marker VEGF. It also decreased the metastatic marker MMP-2. This anticancer effect of BITC was observed in DEN treated mice as well as in hepatoma cell lines. The reported antineoplastic activity was correlated with downregulation of HGF and its downstream molecules pAkt and STAT3. Conclusion: The effect of BITC on HGF /pAkt/ STAT3 axis has a potential role in both chemopreventive and chemotherapeutic effects of BITC.