Diallyl disulfide suppresses FOXM1-mediated proliferation and invasion in osteosarcoma by upregulating miR-134.
J Cell Biochem. 2018 Nov 1. Epub 2018 Nov 1. PMID: 30387181
Diallyl disulfide (DADS), a volatile component of garlic oil, exerts anticancer activity in various types of cancers, while its anticancer effects against osteosarcoma (OS) have not been previously explored. This study aimed to investigate the anticancer potential of DADS in OS and to explore the underlying mechanisms. DADS reduced the cell viability and increased the expression of miR-134 in OS cell lines, and this effect was in a time- and concentration-dependent manner. Furthermore, in vitro functional assays revealed that DADS significantly inhibited the proliferation and invasion of human OS U2OS and MG-63 cells, which was partially reversed by miR-134 inhibitor transfection. DADS exhibited in vivo antitumor activity and upregulated miR-134 expression in xenograft tumors. Downregulation of miR-134 attenuated DADS-induced antitumor capacity. Further bioinformatics prediction analysis revealed that the 3'-untranslated region (3'-UTR) of Forkhead Box M1 (FOXM1) harbored miR-134-binding sites, and overexpression of miR-134 repressed the luciferase activity of the reporting vector containing FOXM1 3'-UTR. Both miR-134 overexpression and DADS inhibited FOXM1 expression in U2OS cells, while enforced expression of FOXM1 suppressed DADS-induced antiproliferation and anti-invasion capacity in U2OS cells. Furthermore, DADS treatment led to significant downregulation of cyclin D1, c-myc, and lymphoid enhancer-binding factor 1 expression, but the remarkably upregulated p21 level in U2OS cells. Collectively, DADS could be a promising anticancer agent for OS, and the underlying mechanisms might be associated with the antiproliferation and anti-invasion properties through upregulating miR-134 expression.