Synergistic antitumor activity of vitamins C and K3 on human urologic tumor cell lines.
A micro-tetrazolium assay was employed to evaluate vitamin C (VC), vitamin K3 (VK3) and vitamin C/vitamin K3 combinations (VC/VK3) for their antitumor activity against eight human urologic tumor cell lines. While the individual vitamins exhibited antitumor activity at high concentrations, co-administration of the vitamins in a VC : VK3 ratio of 100 : 1 potentiated antitumor activity 4- to 61-fold even when exposure times were as short as 1 hour. Administration of exogenous catalase destroyed the antitumor activity of the vitamins and suggested that hydrogen peroxide and perhaps other reactive oxygen species were involved in the antitumor mechanism of these vitamins. Electron micrographs taken in a previous study demonstrated that vitamin treatment damaged mitochondria and may have impaired ATP synthesis. Analysis of cellular 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 levels. These results suggested that redox cycling of the vitamin combination increased oxidative stress until it surpassed the reducing ability of the cellular thiols and cellular or genetic damage ensued.
Department of Urology, Summa Health System, Akron, Ohio 44304, USA.
M
M
Venugopal
J M
JM
Jamison
J
J
Gilloteaux
J A
JA
Koch
M
M
Summers
D
D
Giammar
C
C
Sowick
J L
JL
Summers
D000255:Adenosine Triphosphate / Q000378:metabolism; D001205:Ascorbic Acid / Q000494:pharmacology*; D004261:DNA Replication; D004357:Drug Synergism; D006801:Humans; D008854:Microscopy, Electron; D017382:Reactive Oxygen Species; D013438:Sulfhydryl Compounds / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014565:Urogenital Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D014812:Vitamin K / Q000494:pharmacology*
D017382:Reactive Oxygen Species; D013438:Sulfhydryl Compounds; D014812:Vitamin K; D000255:Adenosine Triphosphate; D001205:Ascorbic Acid