Editors' ChoiceCancer

Getting all stressed out by vitamin C

Sci. Signal.  15 Dec 2015:
Vol. 8, Issue 407, pp. ec376
DOI: 10.1126/scisignal.aae0545

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 the abundance of a certain receptor is increased 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.

J. Yun, E. Mullarky, C. Lu, K. N. Bosch, A. Kavalier, K. Rivera, J. Roper, I. I. C. Chio, E. G. Giannopoulou, C. Rago, A. Muley, J. M. Asara, J. Paik, O. Elemento, Z. Chen, D. J. Pappin, L. E. Dow, N. Papadopoulos, S. S. Gross, L. C. Cantley, Vitamin C selectively kills KRAS and BRAF mutant colorectal cancer cells by targeting GAPDH. Science 350, 1391–1396 (2015). [Abstract] [Full Text]

C. R. Reczek, N. S. Chandel, Revisiting vitamin C and cancer. Science 350, 1317–1318 (2015). [Abstract] [Full Text]