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EnglishA 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.
| Titolo: | Co-carcinogenic effects of vitamin E in prostate | |
| Autore/i: | Vivarelli F.; Canistro D.; Cirillo S.; Papi A.; Spisni E.; Vornoli A.; Croce C. M. D.; Longo V.; Franchi P.; Filippi S.; Lucarini M.; Zanzi C.; Rotondo F.; Lorenzini A.; Marchionni S.; Paolini M. | |
| Autore/i Unibo: | ||
| Anno: | 2019 | |
| Rivista: | ||
| Digital Object Identifier (DOI): | http://dx.doi.org/10.1038/s41598-019-48213-1 | |
| 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. | |
| Data stato definitivo: | 2019-10-23T15:01:52Z | |
| Appare nelle tipologie: | 1.01 Articolo in rivista |
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| File | Descrizione | Tipo | Licenza | |
|---|---|---|---|---|
| vitamin e.pdf | Versione (PDF) editoriale | Licenza per Accesso Aperto. Creative Commons Attribuzione (CCBY) | Open Access Visualizza/Apri |
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