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Its clinical use is limited due to a cumulative dose\u2010dependent and irreversible cardiotoxicity that can cause progressive cardiomyopathy and congestive heart failure. A cardioprotective therapy that can decrease heart damage without reducing the anticancer efficacy during Doxo therapy is of utmost importance. Anthocyanins (ACNs) are renowned cardioprotective agents thanks to their antioxidant and anti\u2010inflammatory properties. An ACN\u2010rich diet from purple corn, which mainly contains cyanidin 3\u2010glucoside (C3G) and its acetylated derivatives, has been previously shown to be effective in reducing Doxo\u2010induced cardiotoxicity in mice. Aiming at unveiling the molecular mechanisms involved in ACN protection, we considered the fibroblast growth factor 21\/AMP\u2010activated protein kinase\/SIRTUIN1 (FGF21\/AMPK\/SIRT1)\/p53 pathway in murine HL\u20101 cardiomyocytes treated with Doxo in the presence or absence of purple corn extract (RED). Our work shows that Doxo\u2010induced AMPK activation is restored to control levels by the RED extract. p53 acetylation was increased by the RED extract and upon Sirt1 silencing, indicating that p53 acetylation is SIRT1\u2010dependent and suggesting that the RED extract may affect SIRT1 activity through AMPK. Notably, increased p53 acetylation led to decreased levels of cleaved\u2010caspase 3 and Puma and p21 transcript levels, indicating a reduced level of apoptosis. The RED\u2010induced cardioprotection and p53 acetylation were confirmed in mouse primary cardiomyocytes. In conclusion, the RED extract may prevent cardiomyocytes apoptosis through the modulation of AMPK and acetylation of p53.<\/jats:p>","DOI":"10.1155\/omcl\/7786043","type":"journal-article","created":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T17:56:21Z","timestamp":1758218181000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Purple Corn Extract Prevents Doxo\u2010Induced Cardiotoxicity by Counteracting AMPK Activation and p53 Acetylation in HL\u20101 and Primary Cardiomyocytes"],"prefix":"10.1155","volume":"2025","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9472-424X","authenticated-orcid":false,"given":"Francesca","family":"Cappellini","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1220-2403","authenticated-orcid":false,"given":"Debora","family":"Zorzan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7396-6496","authenticated-orcid":false,"given":"Federica","family":"Tomay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5897-1673","authenticated-orcid":false,"given":"Marta","family":"Toccaceli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6501-5364","authenticated-orcid":false,"given":"Alessandra","family":"Marinelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Mancini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5303-4242","authenticated-orcid":false,"given":"Annalisa","family":"Bucchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9505-3118","authenticated-orcid":false,"given":"Chiara","family":"Tonelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3318-0442","authenticated-orcid":false,"given":"Katia","family":"Petroni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,18]]},"reference":[{"key":"e_1_2_12_1_2","doi-asserted-by":"publisher","DOI":"10.1159\/000265166"},{"key":"e_1_2_12_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2012.03.006"},{"key":"e_1_2_12_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2919"},{"key":"e_1_2_12_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2013.10.013"},{"key":"e_1_2_12_5_2","doi-asserted-by":"publisher","DOI":"10.1515\/hsz-2016-0316"},{"key":"e_1_2_12_6_2","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2015.00133"},{"key":"e_1_2_12_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2017.410"},{"key":"e_1_2_12_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s13238-011-1063-9"},{"key":"e_1_2_12_9_2","first-page":"245","article-title":"SIRT1 Phosphorylation by AMP-Activated Protein Kinase Regulates p53 Acetylation","volume":"4","author":"Lau A. 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