SYNERGISTIC ANTITUMOR-ACTIVITY OF VITAMIN-C AND VITAMIN-K-3 ON HUMAN UROLOGIC TUMOR-CELL LINES

A micro-tetrazolium assay was employed to evaluate vitamin C (VC), vit amin K-3 (VK3) and vitamin C/vitamin K-3 combinations (VC/VK3) for the ir antitumor activity against eight human urologic tumor cell lines. W hile the individual vitamins exhibited antitumor activity at high conc entrations, co-administration of the vitamin in a VC : VK3 ratio of 10 0 : 1 potentiated antitumor activity 4- to 61-fold even when exposure times were as short as 1 hour. Administration of exogenous catalase de stroyed the antitumor activity of the vitamins and suggested that cata lase destroyed the antitumor activity of the vitamins and suggested th at hydrogen peroxide and perhaps other reactive oxygen species were in volved in the antitumor mechanism of these vitamins. Electron microgra phs taken in a previous study demonstrated that vitamin treatment dama ged mitochondria and may have impaired ATP synthesis. Analysis of cell ular ATP and thiol levels as well as DNA and protein synthesis during the first five hours following a one hour VC/VK3 treatment, revealed: a transient increase in ATP production, a substantial decrease in DNA synthesis, an increase in protein synthesis and a decrease in thiol le vels. These results suggested that redox cycling of the vitamin combin ation increased oxidative stress until it surpassed the reducing abili ty of the cellular thiols and cellular or genetic damage ensured.