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

Author

Listed:
  • Maira Di Tano

    (University of Milan. Department of Oncology and Hemato-Oncology
    IFOM, FIRC Institute of Molecular Oncology)

  • Franca Raucci

    (IFOM, FIRC Institute of Molecular Oncology)

  • Claudio Vernieri

    (IFOM, FIRC Institute of Molecular Oncology
    Fondazione IRCCS Istituto Nazionale Tumori)

  • Irene Caffa

    (University of Genoa
    IRCCS Ospedale Policlinico San Martino)

  • Roberta Buono

    (University of Southern California
    University of California)

  • Maura Fanti

    (University of Southern California)

  • Sebastian Brandhorst

    (University of Southern California)

  • Giuseppe Curigliano

    (University of Milan. Department of Oncology and Hemato-Oncology
    European Institute of Oncology, IRCCS)

  • Alessio Nencioni

    (University of Genoa
    IRCCS Ospedale Policlinico San Martino)

  • Filippo de Braud

    (University of Milan. Department of Oncology and Hemato-Oncology
    Fondazione IRCCS Istituto Nazionale Tumori)

  • Valter D. Longo

    (IFOM, FIRC Institute of Molecular Oncology
    University of Southern California)

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.

Suggested Citation

  • 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, 2020. "Synergistic effect of fasting-mimicking diet and vitamin C against KRAS mutated cancers," Nature Communications, Nature, vol. 11(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16243-3
    DOI: 10.1038/s41467-020-16243-3
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    Cited by:

    1. Laura C. D. Pomatto-Watson & Monica Bodogai & Oye Bosompra & Jonathan Kato & Sarah Wong & Melissa Carpenter & Eleonora Duregon & Dolly Chowdhury & Priya Krishna & Sandy Ng & Emeline Ragonnaud & Robert, 2021. "Daily caloric restriction limits tumor growth more effectively than caloric cycling regardless of dietary composition," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
    2. Amr Khalifa & Ana Guijarro & Silvia Ravera & Nadia Bertola & Maria Pia Adorni & Bianca Papotti & Lizzia Raffaghello & Roberto Benelli & Pamela Becherini & Asmaa Namatalla & Daniela Verzola & Daniele R, 2023. "Cyclic fasting bolsters cholesterol biosynthesis inhibitors’ anticancer activity," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

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