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 and Valter D. Longo ()
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Maira Di Tano: University of Milan. Department of Oncology and Hemato-Oncology
Franca Raucci: IFOM, FIRC Institute of Molecular Oncology
Claudio Vernieri: IFOM, FIRC Institute of Molecular Oncology
Irene Caffa: University of Genoa
Roberta Buono: University of Southern California
Maura Fanti: University of Southern California
Sebastian Brandhorst: University of Southern California
Giuseppe Curigliano: University of Milan. Department of Oncology and Hemato-Oncology
Alessio Nencioni: University of Genoa
Filippo de Braud: University of Milan. Department of Oncology and Hemato-Oncology
Valter D. Longo: IFOM, FIRC Institute of Molecular Oncology

Nature Communications, 2020, vol. 11, issue 1, 1-11

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-16243-3

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