title: The differential NF-kB modulation by S-adenosyl-L-methionine, N-acetylcysteine and quercetin on the promotion stage of chemical hepatocarcinogenesis.
abstract: S-adenosylmethionine (SAM), N-acetylcysteine (NAC) and quercetin exhibit a chemoprotective effect. Likely this effect is mediated by counteracting, oxidative stress and NF-kB activation. To test this hypothesis F344 rats were subjected to hepatocarcinogenesis with or without antioxidants. NAC decreased foci in number and area, SAM and quercetin decreased area. Lipid-peroxidation was decreased by antioxidants, but only SAM increased glutathione. SAM, in its regulation from IKK downwards, abolished the NF-kB activation. NAC decreased IKK and IkB-a phosphorylation, and Rel-A/p65 and NF-kB binding, though the last two were affected with less intensity compared to the NF-kB inhibitor. Quercetin decreased Rel-A/p65, without modifying upstream signalling. Although all antioxidants inhibited oxidative stress as shown by reduction of lipid peroxidation, not all exerted the same effect on NF-kB signalling pathway and only SAM increased GSH. The mechanisms exerted by SAM in the reduction of foci makes this compound a potential liver cancer therapeutic agent.
authors.affiliation: Departamento de Biología Celular, Centro de Investigación y de Estudios Avanzados del IPN, México D.F, México.
authors.forename: Rebeca
authors.initials: R
authors.lastname: García-Román
authors.forename: Daniel
authors.initials: D
authors.lastname: Salazar-González
authors.forename: Sandra
authors.initials: S
authors.lastname: Rosas
authors.forename: Jaime
authors.initials: J
authors.lastname: Arellanes-Robledo
authors.forename: Olga
authors.initials: O
authors.lastname: Beltrán-Ramírez
authors.forename: Samia
authors.initials: S
authors.lastname: Fattel-Fazenda
authors.forename: Saúl
authors.initials: S
authors.lastname: Villa-Treviño
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D005786:Gene Expression Regulation; D015227:Lipid Peroxidation; D008113:Liver Neoplasms / Q000139:chemically induced / Q000209:etiology*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D018384:Oxidative Stress; D011794:Quercetin / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D012436:S-Adenosylmethionine / Q000494:pharmacology*; D015398:Signal Transduction
chemical_list: D000975:Antioxidants; D014408:Biomarkers, Tumor; D016328:NF-kappa B; D012436:S-Adenosylmethionine; D011794:Quercetin; D000111:Acetylcysteine