{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T03:31:03Z","timestamp":1789183863403,"version":"build-2803163510"},"reference-count":182,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,5,10]],"date-time":"2023-05-10T00:00:00Z","timestamp":1683676800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82272601"],"award-info":[{"award-number":["82272601"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["ZR2021MH330"],"award-info":[{"award-number":["ZR2021MH330"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["21330089963007"],"award-info":[{"award-number":["21330089963007"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["82272601"],"award-info":[{"award-number":["82272601"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2021MH330"],"award-info":[{"award-number":["ZR2021MH330"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["21330089963007"],"award-info":[{"award-number":["21330089963007"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Qilu Young Scholar\u2019s Program of Shandong University","award":["82272601"],"award-info":[{"award-number":["82272601"]}]},{"name":"Qilu Young Scholar\u2019s Program of Shandong University","award":["ZR2021MH330"],"award-info":[{"award-number":["ZR2021MH330"]}]},{"name":"Qilu Young Scholar\u2019s Program of Shandong University","award":["21330089963007"],"award-info":[{"award-number":["21330089963007"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Doxorubicin (DOX) is a highly effective chemotherapeutic drug, but its long-term use can cause cardiotoxicity and drug resistance. Accumulating evidence demonstrates that p53 is directly involved in DOX toxicity and resistance. One of the primary causes for DOX resistance is the mutation or inactivation of p53. Moreover, because the non-specific activation of p53 caused by DOX can kill non-cancerous cells, p53 is a popular target for reducing toxicity. However, the reduction in DOX-induced cardiotoxicity (DIC) via p53 suppression is often at odds with the antitumor advantages of p53 reactivation. Therefore, in order to increase the effectiveness of DOX, there is an urgent need to explore p53-targeted anticancer strategies owing to the complex regulatory network and polymorphisms of the p53 gene. In this review, we summarize the role and potential mechanisms of p53 in DIC and resistance. Furthermore, we focus on the advances and challenges in applying dietary nutrients, natural products, and other pharmacological strategies to overcome DOX-induced chemoresistance and cardiotoxicity. Lastly, we present potential therapeutic strategies to address key issues in order to provide new ideas for increasing the clinical use of DOX and improving its anticancer benefits.<\/jats:p>","DOI":"10.3390\/nu15102259","type":"journal-article","created":{"date-parts":[[2023,5,11]],"date-time":"2023-05-11T01:37:09Z","timestamp":1683769029000},"page":"2259","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["p53 at the Crossroads between Doxorubicin-Induced Cardiotoxicity and Resistance: A Nutritional Balancing Act"],"prefix":"10.3390","volume":"15","author":[{"given":"Yuanfang","family":"Guo","sequence":"first","affiliation":[{"name":"School of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan 250012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufeng","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, The First Affiliated Hospital of Shandong First Medical University, Jinan 250014, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangping","family":"Lu","sequence":"additional","affiliation":[{"name":"School of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan 250012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junlian","family":"Gu","sequence":"additional","affiliation":[{"name":"School of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan 250012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2538","DOI":"10.1021\/bi00462a016","article-title":"Structural comparison of anticancer drug-DNA complexes: Adriamycin and daunomycin","volume":"29","author":"Frederick","year":"1990","journal-title":"Biochemistry"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1146\/annurev-biochem-061809-100002","article-title":"New Mechanistic and Functional Insights into DNA Topoisomerases","volume":"82","author":"Chen","year":"2013","journal-title":"Annu. 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