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Synergistic effect of fasting-mimicking diet and vitamin C against KRAS mutated cancers
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Synergistic effect of fasting-mimicking diet and vitamin C against KRAS mutated cancers
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Journal Article
Synergistic effect of fasting-mimicking diet and vitamin C against KRAS mutated cancers
2020
Overview
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.
Fasting diets are emerging as an approach to delay tumor progression and improve cancer therapies. Here, the authors show that the combination of fasting-mimicking diet with vitamin C decreases tumor development and increases chemotherapy efficacy in KRAS-mutant cancer.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
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/ 38
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/ 42
/ 64
/ 64/60
/ 82/29
/ 82/80
/ Animals
/ Ascorbic Acid - pharmacology
/ Cancer
/ Cell Survival - drug effects
/ Diet
/ Fasting
/ Ferritin
/ Genomes
/ Heme
/ Heme Oxygenase-1 - metabolism
/ Humanities and Social Sciences
/ Humans
/ Mimicry
/ mRNA
/ Mutants
/ Phosphorylation - drug effects
/ Proto-Oncogene Proteins p21(ras) - genetics
/ Reactive Oxygen Species - metabolism
/ Science
/ Tumors
