{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T17:05:31Z","timestamp":1790960731671,"version":"4.1.0"},"reference-count":51,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,11,9]],"date-time":"2023-11-09T00:00:00Z","timestamp":1699488000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In tandem with the expanding obesity pandemic, the prevalence of metabolic dysfunction associated steatohepatitis (MASH, formerly known as NASH)\u2010 driven hepatocellular carcinoma (HCC) is predicted to rise globally, creating a significant need for therapeutic interventions. We previously identified the upregulation of apoptosis antagonizing transcription factor (AATF), which is implicated in facilitating the progression from MASH to HCC. The objective of this study was to examine whether the intervention of curcumin could alleviate AATF\u2010mediated MASH, inhibit tumor growth, and elucidate the underlying mechanism. A preclinical murine model mimicking human MASH\u2010HCC was employed, subjecting mice to either a chow diet normal water (CDNW) or western diet sugar water (WDSW) along with very low dose of carbon tetrachloride (CCl<jats:sub>4<\/jats:sub>\u2010 0.2\u2009\u03bcL\/g, weekly). Mice receiving curcumin (CUR) alongside WDSW\/CCl<jats:sub>4<\/jats:sub> exhibited significant improvements, including reduced liver enzymes, dyslipidemia, steatosis, inflammation, and hepatocellular ballooning. Curcumin treatment also suppressed hepatic expression of inflammatory, fibrogenic, and oncogenic markers. Of note, there was a significant reduction in the expression of AATF upon curcumin treatment in WDSW\/CCl<jats:sub>4<\/jats:sub> mice and human HCC cells. In contrast, curcumin upregulated Kruppel\u2010like factor 4 (KLF4) in MASH liver and HCC cells, which is known to downregulate sp1 (specificity protein\u20101) expression. Thus, curcumin treatment effectively inhibited the progression of MASH to HCC by downregulating the expression of AATF via the KLF4\u2010Sp1 signaling pathway. These preclinical findings establish a novel molecular connection between curcumin and AATF in reducing hepatocarcinogenesis, and provide a strong rationale for the development of curcumin as a viable treatment for MASH\u2010HCC in humans.<\/jats:p>","DOI":"10.1002\/jcp.31151","type":"journal-article","created":{"date-parts":[[2023,11,9]],"date-time":"2023-11-09T11:07:08Z","timestamp":1699528028000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Apoptosis antagonizing transcription factor\u2010mediated liver damage and inflammation to cancer: Therapeutic intervention by curcumin in experimental metabolic dysfunction associated steatohepatitis\u2010hepatocellular carcinoma"],"prefix":"10.1002","volume":"239","author":[{"given":"Akshatha N.","family":"Srinivas","sequence":"first","affiliation":[{"name":"Department of Biochemistry CEMR lab, JSS Medical College, JSS Academy of Higher Education and Research Mysuru 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