Year: 2020
Type: article
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.
Source: Nature Communications
Language: English
Topic: Dietary Effects on Health
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,380
Awards: G1161644807, G1170743233, Dietary Restriction, GH/IGF-l & Mechanisms of Cellular Protection and Regeneration, G1753422283, G2030136792, G2054689343, G2162348278, G2629517649, G373645074, G3905250243, G4465263724, G4473527778, G4529777353, G4627437778, Role of Longevity Regulatory Pathways in Age-dependent Macro-molecular Damage in, G5920830311, G6209003156, G6329577288, G6806196278, G7123298761, G8566713044, G9000022502, Southern California Clinical and Translational Science Institute
OpenAlex ID: W3021756656