Apoptosis-inducing activity of vitamin C and vitamin K

Apoptosis-inducing activity of vitamins C and K and of their analogs are re viewed. Vitamin C shows both reducing and oxidizing activities, depending o n the environment in which this vitamin is present. Higher concentrations o f vitamin C induce apoptotic cell death in various tumor cell lines includi ng oral squamous cell carcinoma and salivary gland tumor cell lines, possib ly 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 stre ss or antitumor agent-induced apoptosis. Sodium 5,6-benzylidene-L-ascorbate , intravenous administration of which induces degeneration of human inopera ble tumors and rat hepatocellular carcinoma in vivo, induces apoptotic or n on-apoptotic cell death, depending on the types of target cells. On the oth er hand, elevation of intracellular concentration of ascorbic acid by treat ment with ascorbate 2-phosphate or dehydroascorbic acid makes the cells res istant to the oxidative stress-induced apoptosis. Vitamin K-2, which has a geranylgeranyl group as a side chain, and vitamin K-3 induces apoptosis of various cultured cells including osteoclasts and osteoblasts, by elevating peroxide and superoxide radicals. Synergistic apoptosis-inducing actions ha ve been found between vitamins C and K, and between these vitamins and anti proliferative agents. The possible therapeutic application of these vitamin s is discussed.