Cytotoxic activity of vitamins K1, K2 and K3 against human oral tumor cell lines.
Vitamin K1, K2 and K3 were compared for their cytotoxic activity, radical generation and O2- scavenging activity. Among these compounds, vitamin K3 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 K3 induced internucleosomal DNA fragmentation in HL-60 cells, but not in HSC-2 or HSG cells. The cytotoxic activity of vitamins K2 and K1 was one and two orders lower, respectively, than K3. Vitamin K2, but not vitamin K3, showed tumor-specific cytotoxic action. ESR spectroscopy showed that only vitamin K3 produced radical(s) under alkaline condition and most potently enhanced the radical intensity of sodium ascorbate and scavenged O2- (generated by hypoxanthine-xanthine oxidase reaction system); vitamin K2 was much less active whereas vitamin K1 was inactive. These data suggest that the cytotoxic activity of vitamin K3 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.
Okayasu
H
H
Department of Dental Pharmacology, Meikai University School of Dentistry, Sakado, Saitama, Japan.
Ishihara
M
M
Satoh
K
K
Sakagami
H
H
D002294:Carcinoma, Squamous Cell / Q000188:drug therapy; D053938:DNA Fragmentation / Q000187:drug effects; D004578:Electron Spin Resonance Spectroscopy; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D016166:Free Radical Scavengers / Q000633:toxicity; D005881:Gingiva / Q000166:cytology / Q000187:drug effects; D018922:HL-60 Cells / Q000187:drug effects; D006801:Humans; D008958:Models, Molecular; D009062:Mouth Neoplasms / Q000188:drug therapy*; D012468:Salivary Gland Neoplasms / Q000188:drug therapy; D013329:Structure-Activity Relationship; D013481:Superoxides / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014812:Vitamin K / Q000633:toxicity*; D010837:Vitamin K 1 / Q000633:toxicity; D024482:Vitamin K 2 / Q000633:toxicity; D024483:Vitamin K 3 / Q000633:toxicity
D016166:Free Radical Scavengers; D024482:Vitamin K 2; D013481:Superoxides; D014812:Vitamin K; D024483:Vitamin K 3; D010837:Vitamin K 1