{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T20:05:16Z","timestamp":1788206716800,"version":"build-2803163510"},"reference-count":178,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,1,25]],"date-time":"2022-01-25T00:00:00Z","timestamp":1643068800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014810","name":"Fondazione di Sardegna","doi-asserted-by":"publisher","award":["SimileFdS2016"],"award-info":[{"award-number":["SimileFdS2016"]}],"id":[{"id":"10.13039\/100014810","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014810","name":"Fondazione di Sardegna","doi-asserted-by":"publisher","award":["Pascale FdS2016"],"award-info":[{"award-number":["Pascale FdS2016"]}],"id":[{"id":"10.13039\/100014810","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Alterations of methionine cycle in steatohepatitis, cirrhosis, and hepatocellular carcinoma induce MAT1A decrease and MAT2A increase expressions with the consequent decrease of S-adenosyl-L-methionine (SAM). This causes non-alcoholic fatty liver disease (NAFLD). SAM administration antagonizes pathological conditions, including galactosamine, acetaminophen, and ethanol intoxications, characterized by decreased intracellular SAM. Positive therapeutic effects of SAM\/vitamin E or SAM\/ursodeoxycholic acid in animal models with NAFLD and intrahepatic cholestasis were not confirmed in humans. In in vitro experiments, SAM and betaine potentiate PegIFN-alpha-2a\/2b plus ribavirin antiviral effects. SAM plus betaine improves early viral kinetics and increases interferon-stimulated gene expression in patients with viral hepatitis non-responders to pegIFN\u03b1\/ribavirin. SAM prevents hepatic cirrhosis, induced by CCl4, inhibits experimental tumors growth and is proapoptotic for hepatocellular carcinoma and MCF-7 breast cancer cells. SAM plus Decitabine arrest cancer growth and potentiate doxorubicin effects on breast, head, and neck cancers. Furthermore, SAM enhances the antitumor effect of gemcitabine against pancreatic cancer cells, inhibits growth of human prostate cancer PC-3, colorectal cancer, and osteosarcoma LM-7 and MG-63 cell lines; increases genomic stability of SW480 cells. SAM reduces colorectal cancer progression and inhibits the proliferation of preneoplastic rat liver cells in vivo. The discrepancy between positive results of SAM treatment of experimental tumors and modest effects against human disease may depend on more advanced human disease stage at moment of diagnosis.<\/jats:p>","DOI":"10.3390\/cells11030409","type":"journal-article","created":{"date-parts":[[2022,1,25]],"date-time":"2022-01-25T20:44:33Z","timestamp":1643143473000},"page":"409","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":79,"title":["S-Adenosylmethionine: From the Discovery of Its Inhibition of Tumorigenesis to Its Use as a Therapeutic Agent"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7612-3646","authenticated-orcid":false,"given":"Rosa M.","family":"Pascale","sequence":"first","affiliation":[{"name":"Department of Medical, Surgical and Experimental Sciences, Division of Experimental Pathology and Oncology, University of Sassari, 07100 Sassari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria M.","family":"Simile","sequence":"additional","affiliation":[{"name":"Department of Medical, Surgical and Experimental Sciences, Division of Experimental Pathology and Oncology, University of Sassari, 07100 Sassari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego F.","family":"Calvisi","sequence":"additional","affiliation":[{"name":"Department of Medical, Surgical and Experimental Sciences, Division of Experimental Pathology and Oncology, University of Sassari, 07100 Sassari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4475-3405","authenticated-orcid":false,"given":"Claudio F.","family":"Feo","sequence":"additional","affiliation":[{"name":"Department of Medical, Surgical and Experimental Sciences, Division of Surgery, University of Sassari, 07100 Sassari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Feo","sequence":"additional","affiliation":[{"name":"Department of Medical, Surgical and Experimental Sciences, Division of Experimental Pathology and Oncology, University of Sassari, 07100 Sassari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1016\/S0021-9258(18)44891-0","article-title":"Activation of methionine for transmethylation","volume":"189","author":"Cantoni","year":"1951","journal-title":"J. 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