Apoptosis-inducing activity of vitamin C and vitamin K.
Apoptosis-inducing activity of vitamins C and K and of their analogs are reviewed. Vitamin C shows both reducing and oxidizing activities, depending on the environment in which this vitamin is present. Higher concentrations of vitamin C induce apoptotic cell death in various tumor cell lines including oral squamous cell carcinoma and salivary gland tumor cell lines, possibly via its prooxidant action. The apoptosis-inducing activity of ascorbate is stimulated by Cu2+, lignin and ion chelator, and inhibited by catalase, Fe3+, Co2+ and saliva. On the other hand, at lower concentrations, ascorbic acid displays an antioxidant property, preventing the spontaneous and stress or antitumor agent-induced apoptosis. Sodium 5,6-benzylidene-L-ascorbate, intravenous administration of which induces degeneration of human inoperable tumors and rat hepatocellular carcinoma in vivo, induces apoptotic or non-apoptotic cell death, depending on the types of target cells. On the other hand, elevation of intracellular concentration of ascorbic acid by treatment with ascorbate 2-phosphate or dehydroascorbic acid makes the cells resistant to the oxidative stress-induced apoptosis. Vitamin K2, which has a geranylgeranyl group as a side chain,and vitamin K3 induces apoptosis of various cultured cells including osteoclasts and osteoblasts, by elevating peroxide and superoxide radicals. Synergistic apoptosis-inducing actions have been found between vitamins C and K, and between these vitamins and antiproliferative agents. The possible therapeutic application of these vitamins is discussed.
Sakagami
H
H
Department of Dental Pharmacology, Meikai University School of Dentistry, Sakado, Saitama, Japan. sakagami@dent.meikai.ac.jp
Satoh
K
K
Hakeda
Y
Y
Kumegawa
M
M
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001205:Ascorbic Acid / Q000031:analogs & derivatives / Q000494:pharmacology*; D015519:Bone Density / Q000187:drug effects; D006801:Humans; D015394:Molecular Structure; D051381:Rats; D014407:Tumor Cells, Cultured; D014812:Vitamin K / Q000031:analogs & derivatives / Q000494:pharmacology*
D000975:Antioxidants; D014812:Vitamin K; D001205:Ascorbic Acid