Vitamin C selectively kills KRAS and BRAF mutant colorectal cancer cells by targeting GAPDH.
Level 5 - mechanism / opinion, no new human data
Preclinical in vitro cell culture and animal research with no human clinical data
PubMed 26541605 · doi:10.1126/science.aaa5004
What was done
Investigators treated cultured human colorectal cancer (CRC) cells harboring KRAS or BRAF mutations, as well as wild-type controls, with high levels of vitamin C to evaluate cell survival and metabolic pathways. They examined uptake of dehydroascorbate (DHA) via the GLUT1 transporter, glutathione depletion, reactive oxygen species accumulation, and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) activity. They further tested the effect of high-dose vitamin C on tumor growth in Apc/Kras(G12D) mutant mice.
What was found
The abstract reports no numerical data, effect sizes, or sample sizes. Qualitatively, exposure to high levels of vitamin C selectively killed KRAS- and BRAF-mutant CRC cells compared to wild-type cells. Increased DHA uptake via GLUT1 depleted intracellular glutathione, increased reactive oxygen species, and inactivated GAPDH, causing an energetic crisis in mutant cells. High-dose vitamin C also impaired tumor growth in Apc/Kras(G12D) mutant mice.
Why it matters
It provides a direct mechanistic rationale for testing high-dose vitamin C in colorectal cancers carrying KRAS or BRAF mutations, which are often refractory to approved targeted therapies.
Limits
Findings are entirely preclinical, derived from cell cultures and mouse models; human clinical efficacy, pharmacokinetics, and safety cannot be inferred. The abstract provides no quantitative data, doses, or sample sizes.
Cited by
- supports In vitro studies show that importing dehydroascorbic acid into cancer cells induces oxidative stress and decreases cancer cell viability.