Vitamin C selectively kills <i>KRAS</i> and <i>BRAF</i> mutant colorectal cancer cells by targeting GAPDH

TLDR

Vitamin C has been debated as a cancer therapy, but its mechanistic effects on cancer cells remain poorly understood. The study investigates whether vitamin C’s selective toxicity toward KRAS or BRAF mutant colorectal cancer cells can be therapeutically exploited. Mutant cells up‑regulate a receptor that imports oxidized vitamin C (dehydroascorbate), causing oxidative stress that inactivates the glycolytic enzyme GAPDH essential for their growth, leading to cell death. The authors found that KRAS or BRAF mutant colorectal cancer cells handle vitamin C differently, resulting in selective killing of these cells. Yun et al., Science, this issue p.

Abstract

Getting all stressed out by vitamin C Few experimental cancer therapies have incited as much debate as vitamin C. Yet the mechanistic effect of vitamin C on cancer cells is still poorly understood. Yun et al. studied human colorectal cancer cells with KRAS or BRAF mutations and found that they “handle” vitamin C in a different way than other cells, ultimately to their detriment (see the Perspective by Reczek and Chandel). Because a certain receptor is up-regulated in the mutant cells, they take up the oxidized form of vitamin C (dehydroascorbate). This leads to oxidative stress, inactivation of a glycolytic enzyme required by the mutant cells for growth, and finally cell death. Whether the selective toxicity of vitamin C to these mutant cells can be exploited therapeutically remains unclear. Science , this issue p. 1391 ; see also p. 1317