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.

Synergistic effect of fasting-mimicking diet and vitamin C against KRAS mutated cancers / 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. - In: NATURE COMMUNICATIONS. - ISSN 2041-1723. - 11:1(2020 May 11). [10.1038/s41467-020-16243-3]

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

M. Di Tano
Primo
;
C. Vernieri;M. Fanti;G. Curigliano
Conceptualization
;
A. Nencioni;F. de Braud
Penultimo
;
2020

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.
Animals; Ascorbic Acid; Cell Death; Cell Line, Tumor; Cell Survival; 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; Diet
Settore MED/06 - Oncologia Medica
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/824707
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