Synergistic effect of fasting-mimicking diet and vitamin C against KRAS mutated cancers.

Maira Di Tano, Franca Raucci, Claudio Vernieri, Irene Caffa, Roberta Buono, Maura Fanti, Sebastian Brandhorst, Giuseppe Curigliano, Alessio Nencioni, Filippo de Braud, Valter D. Longo

Research output: Contribution to journalArticlepeer-review

Abstract

Fasting-mimicking diets delay tumor progression and sensitize a wide range of tumors to chemotherapy, but their therapeutic potential in combination with non-cytotoxic compounds is poorly understood. Here we show that vitamin C anticancer activity is limited by the up-regulation of the stress-inducible protein heme-oxygenase-1. The fasting-mimicking diet selectivity reverses vitamin C-induced up-regulation of heme-oxygenase-1 and ferritin in KRAS-mutant cancer cells, consequently increasing reactive iron, oxygen species, and cell death; an effect further potentiated by chemotherapy. In support of a potential role of ferritin in colorectal cancer progression, an analysis of The Cancer Genome Atlas Database indicates that KRAS mutated colorectal cancer patients with low intratumor ferritin mRNA levels display longer 3- and 5-year overall survival. Collectively, our data indicate that the combination of a fasting-mimicking diet and vitamin C represents a promising low toxicity intervention to be tested in randomized clinical trials against colorectal cancer and possibly other KRAS mutated tumors.
Original languageEnglish
Pages (from-to)2332
Number of pages1
JournalNat. Commun.
Volume11
Issue number1
DOIs
Publication statusPublished - May 1 2020

Keywords

  • Humans
  • Disease Progression
  • Survival Analysis
  • Cell Line
  • Tumor
  • Animals
  • *Diet
  • Cell Survival/drug effects
  • Phosphorylation/drug effects
  • Fasting/*physiology
  • Ascorbic Acid/*pharmacology
  • Cell Death/drug effects
  • Heme Oxygenase-1/metabolism
  • Iron/metabolism
  • Mice
  • Inbred BALB C
  • Mutation/*genetics
  • Oxaliplatin/pharmacology
  • Proto-Oncogene Proteins p21(ras)/*genetics
  • Reactive Oxygen Species/metabolism
  • Transferrin/metabolism

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