Allyl isothiocyanate suppressed the proliferation of oral squamous cell carcinoma in vitro, in vivo, and in patient-derived tumor xenografts by downregulating the KDM8/CCNA1 axis

Abstract

Abstract Background: Previous studies have shown that many cruciferous vegetables have anticancer effects, which can be connected with the presence of allyl isothiocyanate (AITC). Histone demethylase KDM8 and cyclin A1 (CCNA1) were required for cell cycle G2/M progression. AITC could induce G2/M arrest of various types of human cancer cells. We aimed to validate KDM8 as a target of the antitumor effects of AITC in patient-derived tumor xenograft (PDTX) models of oral squamous cell carcinoma (OSCC). Methods: The expression of KDM8 was assessed through tissue microarray (TMA) immunohistochemistry (IHC) assay. The effects of AITC on the expression of KDM8 and cell proliferation were investigated in OSCC cell lines, in PDTX models, and SAS subcutaneous xenograft tumors. Results: KDM8 was overexpressed in OSCC. AITC repressed the tumor growth of OSCC PDTX and SAS subcutaneous xenograft. Furthermore, AITC downregulated the expression of KDM8 and CCNA1 and induced histone H3K36me2 expression in oral cancer cells. Conclusions: AITC exerts anticancer effects on oral cancer by inducing cell cycle arrest via inhibiting the KDM8-CCNA1 axis.