The Hypoxia-inducible Factor Renders Cancer Cells More Sensitive to Vitamin C-induced Toxicity

Abstract

Background:There is renewed interest in the possibility of using Vc as an anticancer agent. Results: Activation of HIF triggers a Warburg effect that renders cancer cells more sensitive to Vc-induced toxicity. Conclusion: These results provide a link between the metabolic state and the susceptibility to Vc. Significance: Our work helps to understand the preferential toxicity of Vc toward cancer cells.

GSTO1*C/GSTO2*G haplotype is associated with risk of transitional cell carcinoma of urinary bladder

“…Indeed, we found that smoker carriers of GSTO2*G/G genotype were at approximately fourfold increased TCC risk. It is important to note that in addition to its antioxidant role, ascorbic acid (vitamin C) is also involved in regulation of hypoxia-inducible factor (HIF)-1, a transcription factor that regulates many genes responsible for tumor growth, energy metabolism and apoptosis [20]. In that context, recent data speculates that vitamin C-dependent inhibition of the HIF pathway may provide additional approach for controlling tumor progression and inflammation [21].…”

Combination of Cold Atmospheric Plasma and Vitamin C Effectively Disrupts Bacterial Biofilms

“…Vitamin C has also been suggested to have adverse effects on cancer cells [28]. Hypoxia, often encountered in tumors, made multiple cancer cell lines more susceptible to oxidative damage caused by high doses of vitamin C [29]. Some colorectal cancers carry specific mutations that make them specifically sensitive to vitamin C-induced oxidative stress, i.e.…”

Ascorbic Acid in Cancer: A Renewed Hope?

“…However, the normal cells were spared from this pro-oxidant effect (Warburg effect). This mechanism of selective destruction of cancer cells was further enhanced synergistically by the activation of hypoxia-inducible factor (HIF) [20]. Thus, directly altering intracellular pathways and marking the abnormal clones as targets for immune cells is the second line of defense conferred by AA (Figure 1, light …”