The differential NF-kB modulation by S-adenosyl-L-methionine, N-acetylcysteine and quercetin on the promotion stage of chemical hepatocarcinogenesis

Free Radical Research
Rebeca García-RománSaúl Villa-Treviño

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.

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Citations

Mar 9, 2010·Experimental & Molecular Medicine·Min Kyong MoonHong Kyu Lee
Feb 10, 2012·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Maddalena FrauRosa M Pascale
Feb 11, 2012·Journal of Animal Physiology and Animal Nutrition·A Y AuC G Frondoza
Feb 1, 2012·Toxicologic Pathology·Olga Beltrán-RamírezSaúl Villa-Treviño
Nov 22, 2018·Journal of Animal Physiology and Animal Nutrition·Johanna O ZeitzKlaus Eder
Jan 8, 2021·Molecular Neurobiology·G MorrisB K Puri
Sep 12, 2019·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Gerwyn MorrisMichael Berk
May 8, 2020·Experimental Neurology·Iván Alquisiras-BurgosPenélope Aguilera

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