Vitamin C selectively kills KRAS and BRAF mutant colorectal cancer cells by targeting GAPDH

Abstract

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.

Document Details

Document Type
Pub Defense Publication
Publication Date
Dec 11, 2015
Source ID
10.1126/science.aaa5004

Entities

People

  • Adam Kavalier
  • Ashlesha Muley
  • Carlo Rago
  • Changyuan Lu
  • Darryl J. Pappin
  • Edouard Mullarky
  • Eugenia G. Giannopoulou
  • Iok In Christine Chio
  • Jatin Roper
  • Jihye Paik
  • Jihye Yun
  • John M Asara
  • Kaitlyn N. Bosch
  • Keith Rivera
  • Lewis C. Cantley
  • Lukas E Dow
  • Nickolas Papadopoulos
  • Olivier Elemento
  • Steven S. Gross
  • Zhengming Chen

Organizations

  • Cold Spring Harbor Laboratory
  • Damon Runyon Cancer Research Foundation
  • Harvard Medical School
  • National Cancer Institute
  • National Institutes of Health
  • Tufts Medical Center
  • United States Department of Defense
  • Weill Cornell Medicine

Tags

Fields of Study

  • Biology

Readers

  • Molecular and Cellular Biology
  • Oncology
  • Prostate Cancer Biology.