ArticleThe Biochemical journal2002
Ascorbate up-regulates MLH1 (Mut L homologue-1) and p73: implications for the cellular response to DNA damage.
Article in The Biochemical journal, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 49 citations in OpenAlex.
- Serum vitamin C and other biomarkers differ by genotype of phase 2 enzyme genes GSTM1 and GSTT1.The American journal of clinical nutrition · 2011Trial
- Platinum drugs and taxanes: can we overcome resistance?Cell death discovery · 2021Review
- Pro- and Antioxidant Effects of Vitamin C in Cancer in correspondence to Its Dietary and Pharmacological Concentrations.Oxidative medicine and cellular longevity · 2019Review
- Biochemical changes associated with ascorbic acid-cisplatin combination therapeutic efficacy and protective effect on cisplatin-induced toxicity in tumor-bearing mice.Toxicology reports · 2015Article
- Glutathione S-transferase T1, O1 and O2 polymorphisms are associated with survival in muscle invasive bladder cancer patients.PloS one · 2013Article
- Mechanisms of Cisplatin-Induced Apoptosis and of Cisplatin Sensitivity: Potential of BIN1 to Act as a Potent Predictor of Cisplatin Sensitivity in Gastric Cancer Treatment.International journal of surgical oncology · 2012Article
- Molecular and cellular pathways associated with chromosome 1p deletions during colon carcinogenesis.Clinical and experimental gastroenterology · 2011Article
- Modulation of histone methylation and MLH1 gene silencing by hexavalent chromium.Toxicology and applied pharmacology · 2009Article
- The ubiquitin-protein ligase Itch regulates p73 stability.The EMBO journal · 2005Article
- PIAS-1 is a checkpoint regulator which affects exit from G1 and G2 by sumoylation of p73.Molecular and cellular biology · 2004Article
- p73alpha is a candidate effector in the p53 independent apoptosis pathway of cisplatin damaged primary murine colonocytes.Journal of clinical pathology · 2004Article
- Micronuclei to detect in vivo chemotherapy damage in a p53 mutated solid tumour.British journal of cancer · 2003Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
We have found previously that ascorbic acid (vitamin C), as well as acting as a radical scavenger, may modulate the expression of several genes [i.e. fra-1, glutathione S-transferase Pi (GSTpi) and Mut L homologue-1 (MLH1)] in human keratinocytes. In the present paper, we demonstrate that MLH1, as well as its downstream target p73, can be positively modulated by this antioxidant vitamin, indeed, up-regulation of the two mRNAs was observed after just 2 h, and increased further up to 16 h of treatment. Modulation of MLH1 and p73 gene expression improves cellular susceptibility to apoptosis triggered by the DNA-damaging agent cisplatin. Indeed, in ascorbate-supplemented cells, increased cisplatin-induced apoptosis was seen, involving activation of the MLH1/c-Abl/p73 signalling cascade. Our results were further confirmed by studies performed on genetically defined mutants, i.e. mouse embryo fibroblasts derived from knock-out animals for c-Abl or p53, as well as human colon carcinoma cell lines deficient in MLH1. The increased sensitivity to cisplatin observed in ascorbate-loaded cells appeared to be dependent exclusively on MLH1 and c-Abl expression, and independent of p53. These data suggest a potential mechanism accounting for the anti-carcinogenic and anti-cancer activities of vitamin C.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.