Synergistic effect of fasting-mimicking diet and vitamin C against KRAS mutated cancers: Nature Communications

M. Di Tano, F. Raucci, C. Vernieri, I. Caffa, R. Buono, M. Fanti, S. Brandhorst, G. Curigliano, A. Nencioni, F. de Braud, V.D. Longo

Research output: Contribution to journalArticlepeer-review


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. © 2020, The Author(s).
Original languageEnglish
JournalNat. Commun.
Issue number1
Publication statusPublished - 2020


  • acetylcysteine
  • aflatoxin B1
  • ascorbic acid
  • ceruloplasmin
  • deferoxamine
  • doxorubicin
  • ferritin
  • glutathione
  • histone H2AX
  • iron
  • K ras protein
  • messenger RNA
  • oxaliplatin
  • protoporphyrin
  • reduced nicotinamide adenine dinucleotide (phosphate) dehydrogenase (quinone)
  • superoxide dismutase
  • transcription factor Nrf2
  • heme oxygenase 1
  • KRAS protein, human
  • protein p21
  • reactive oxygen metabolite
  • transferrin
  • cancer
  • cell component
  • chemotherapy
  • diet
  • enzyme
  • enzyme activity
  • mutation
  • protein
  • RNA
  • toxicity
  • tumor
  • animal welfare
  • antineoplastic activity
  • Article
  • cancer growth
  • cell death
  • cell viability
  • cell viability assay
  • chemical reaction kinetics
  • cytotoxicity
  • flow cytometry
  • gene expression
  • genetic transfection
  • human
  • human cell
  • immunoblotting
  • immunoprecipitation
  • iron binding capacity
  • metastasis
  • overall survival
  • oxidative stress
  • priority journal
  • protein expression
  • protein phosphorylation
  • real time polymerase chain reaction
  • RNA extraction
  • RNA interference
  • synergistic effect
  • tumor growth
  • tumor immunity
  • tumor volume
  • tumor xenograft
  • upregulation
  • Western blotting
  • animal
  • Bagg albino mouse
  • cell survival
  • diet restriction
  • disease exacerbation
  • drug effect
  • genetics
  • metabolism
  • phosphorylation
  • physiology
  • survival analysis
  • tumor cell line
  • Animals
  • Ascorbic Acid
  • Cell Death
  • Cell Line, Tumor
  • Cell Survival
  • Diet
  • Disease Progression
  • Fasting
  • Heme Oxygenase-1
  • Humans
  • Iron
  • Mice, Inbred BALB C
  • Mutation
  • Oxaliplatin
  • Phosphorylation
  • Proto-Oncogene Proteins p21(ras)
  • Reactive Oxygen Species
  • Survival Analysis
  • Transferrin


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