Synergistic cytotoxic action of vitamin C and vitamin K3

Anticancer Res. 2001 Sep-Oct;21(5):3439-44.


We investigated the combination effect of sodium ascorbate (vitamin C) and menadione (vitamin K3) on the viability of various cultured cells. Human oral squamous cell carcinoma (HSC-2, HSC-3) and human promyelocytic leukemia (HL-60) cells were more sensitive to these vitamins as compared to normal cells (human gingival fibroblast HGF, human periodontal ligament fibroblast HPLF, human pulp cell HPC). The combination of vitamin C and vitamin K3 produced synergistic cytotoxicity against all these 6 cell lines. Treatment with vitamin C or vitamin K3, or their combination, induced internucleosomal DNA fragmentation only in HL-60 cells, but not in the oral tumor cell lines (HSC-2, HSC-3, HSG). ESR spectroscopy showed that vitamins C and K3 produce radicals under alkaline conditions and that the combination of these two vitamins synergistically enhanced their respective radical intensities.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Ascorbic Acid / administration & dosage
  • Ascorbic Acid / pharmacology*
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / metabolism
  • DNA Fragmentation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Electron Spin Resonance Spectroscopy
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • HL-60 Cells / drug effects
  • HL-60 Cells / metabolism
  • Humans
  • Mouth Neoplasms / drug therapy
  • Mouth Neoplasms / metabolism
  • Tumor Cells, Cultured
  • Vitamin K 3 / administration & dosage
  • Vitamin K 3 / pharmacology*


  • Vitamin K 3
  • Ascorbic Acid