The differential NF-kB modulation by S-adenosyl-L-methionine, N-acetylcysteine and quercetin on the promotion stage of chemical hepatocarcinogenesis.
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.
García-Román
Rebeca
R
Departamento de Biología Celular, Centro de Investigación y de Estudios Avanzados del IPN, México D.F, México.
Salazar-González
Daniel
D
Rosas
Sandra
S
Arellanes-Robledo
Jaime
J
Beltrán-Ramírez
Olga
O
Fattel-Fazenda
Samia
S
Villa-Treviño
Saúl
S
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
D000975:Antioxidants; D014408:Biomarkers, Tumor; D016328:NF-kappa B; D012436:S-Adenosylmethionine; D011794:Quercetin; D000111:Acetylcysteine