Co-carcinogenic effects of vitamin E in prostate

Autor: Fabio Vivarelli, Donatella Canistro, Silvia Cirillo, Alessio Papi, Enzo Spisni, Andrea Vornoli, Clara M. Della Croce, Vincenzo Longo, Paola Franchi, Sandra Filippi, Marco Lucarini, Cristina Zanzi, Francesca Rotondo, Antonello Lorenzini, Silvia Marchionni, Moreno Paolini
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: Scientific Reports, Vol 9, Iss 1, Pp 1-10 (2019)
Druh dokumentu: article
ISSN: 2045-2322
DOI: 10.1038/s41598-019-48213-1
Popis: Abstract A large number of basic researches and observational studies suggested the cancer preventive activity of vitamin E, but large-scale human intervention trials have yielded disappointing results and actually showed a higher incidence of prostate cancer although the mechanisms underlying the increased risk remain largely unknown. Here we show through in vitro and in vivo studies that vitamin E produces a marked inductive effect on carcinogen-bioactivating enzymes and a pro-oxidant status promoting both DNA damage and cell transformation frequency. First, we found that vitamin E in the human prostate epithelial RWPE-1 cell line has the remarkable ability to upregulate the expression of various phase-I activating cytochrome P450 (CYP) enzymes, including activators of polycyclic aromatic hydrocarbons (PAHs), giving rise to supraphysiological levels of reactive oxygen species. Furthermore, our rat model confirmed that vitamin E in the prostate has a powerful booster effect on CYP enzymes associated with the generation of oxidative stress, thereby favoring lipid-derived electrophile spread that covalently modifies proteins. We show that vitamin E not only causes DNA damage but also promotes cell transformation frequency induced by the PAH-prototype benzo[a]pyrene. Our findings might explain why dietary supplementation with vitamin E increases the prostate cancer risk among healthy men.
Databáze: Directory of Open Access Journals
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