Cytotoxic activity of vitamins K1, K2 and K3 against human oral tumor cell lines

Vitamin K-1, K-2 and K-3 were compared for their cytotoxic activity, radical generation and O-2(-) scavenging activity. Among these compounds, vitamin K-3 showed the highest cytotoxic activity against human oral tumor cell lines (HSC-2, HSG), human promyelocytic leukemic cell line (HL-60) and human gingival fibroblast (HGF). Vitamin K-3 induced internucleosomal DNA fragmentation in HL-60 cells, but not in HSC-2 or HSG cells. The cytotoxic activity of vitamins K-2 and K-1 was one and two orders lower, respectively, than K-3. Vitamin K-2, but not vitamin K-3 showed tumor-specific cytotoxic action. ESR spectroscopy showed that only vitamin K-3 produced radical(s) under alkaline condition and most potently enhanced the radical intensity of sodium ascorbate and scavenged O-2(-) (generated by hypoxanthine-xanthine oxidase reaction system); vitamin K-2 was much less active whereas vitamin K-1 was inactive. These data suggest that the cytotoxic activity of vitamin K-3 is generated by radical-mediated oxidation mechanism and that this vitamin has two opposing actions (that is, antioxidant and prooxidant), depending on the experimental conditions.