p53 at the Crossroads between Doxorubicin-Induced Cardiotoxicity and Resistance: A Nutritional Balancing Act

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 inactiva...

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Main Authors: Yuanfang Guo, Yufeng Tang, Guangping Lu, Junlian Gu
Format: Article
Language:English
Published: MDPI AG 2023-05-01
Series:Nutrients
Subjects:
Online Access:https://www.mdpi.com/2072-6643/15/10/2259
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author Yuanfang Guo
Yufeng Tang
Guangping Lu
Junlian Gu
author_facet Yuanfang Guo
Yufeng Tang
Guangping Lu
Junlian Gu
author_sort Yuanfang Guo
collection DOAJ
description 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.
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spelling doaj.art-1043419f1aaa420d99658535dcfd1a4c2023-11-18T02:43:55ZengMDPI AGNutrients2072-66432023-05-011510225910.3390/nu15102259p53 at the Crossroads between Doxorubicin-Induced Cardiotoxicity and Resistance: A Nutritional Balancing ActYuanfang Guo0Yufeng Tang1Guangping Lu2Junlian Gu3School of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan 250012, ChinaDepartment of Orthopedic Surgery, The First Affiliated Hospital of Shandong First Medical University, Jinan 250014, ChinaSchool of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan 250012, ChinaSchool of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan 250012, ChinaDoxorubicin (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.https://www.mdpi.com/2072-6643/15/10/2259p53DOX-induced cardiotoxicityDOX resistancedietary nutrientsnatural products
spellingShingle Yuanfang Guo
Yufeng Tang
Guangping Lu
Junlian Gu
p53 at the Crossroads between Doxorubicin-Induced Cardiotoxicity and Resistance: A Nutritional Balancing Act
Nutrients
p53
DOX-induced cardiotoxicity
DOX resistance
dietary nutrients
natural products
title p53 at the Crossroads between Doxorubicin-Induced Cardiotoxicity and Resistance: A Nutritional Balancing Act
title_full p53 at the Crossroads between Doxorubicin-Induced Cardiotoxicity and Resistance: A Nutritional Balancing Act
title_fullStr p53 at the Crossroads between Doxorubicin-Induced Cardiotoxicity and Resistance: A Nutritional Balancing Act
title_full_unstemmed p53 at the Crossroads between Doxorubicin-Induced Cardiotoxicity and Resistance: A Nutritional Balancing Act
title_short p53 at the Crossroads between Doxorubicin-Induced Cardiotoxicity and Resistance: A Nutritional Balancing Act
title_sort p53 at the crossroads between doxorubicin induced cardiotoxicity and resistance a nutritional balancing act
topic p53
DOX-induced cardiotoxicity
DOX resistance
dietary nutrients
natural products
url https://www.mdpi.com/2072-6643/15/10/2259
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AT guangpinglu p53atthecrossroadsbetweendoxorubicininducedcardiotoxicityandresistanceanutritionalbalancingact
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