Natural products targeting regulated cell deaths for adriamycin-induced cardiotoxicity

Abstract Adriamycin (ADR), as an anti-cancer drug in routine clinical application, is utilized to treat various cancers such as ovarian cancer, hematological malignant tumor, and endometrial carcinoma. However, its serious dose-dependent cardiotoxicity extremely limits its clinical application. Curr...

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Main Authors: Zheng Wang, Yanli Zhu, Yu Yao, Wenyu Zhang, Bo Wang, Jing Wang, Yang Yang, Liwen Liu
Format: Article
Language:English
Published: Nature Publishing Group 2025-03-01
Series:Cell Death Discovery
Online Access:https://doi.org/10.1038/s41420-025-02389-w
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author Zheng Wang
Yanli Zhu
Yu Yao
Wenyu Zhang
Bo Wang
Jing Wang
Yang Yang
Liwen Liu
author_facet Zheng Wang
Yanli Zhu
Yu Yao
Wenyu Zhang
Bo Wang
Jing Wang
Yang Yang
Liwen Liu
author_sort Zheng Wang
collection DOAJ
description Abstract Adriamycin (ADR), as an anti-cancer drug in routine clinical application, is utilized to treat various cancers such as ovarian cancer, hematological malignant tumor, and endometrial carcinoma. However, its serious dose-dependent cardiotoxicity extremely limits its clinical application. Currently, there remains a dearth of therapeutic agents to mitigate ADR-induced cardiotoxicity. Extensive research has demonstrated that ADR can simultaneously trigger various regulated cell death (RCD) pathways, such as apoptosis, autophagy, ferroptosis, necroptosis, and pyroptosis. Therefore, drugs targeting these RCD pathways may represent effective strategies for treating ADR-induced cardiotoxicity. Natural products, with their wide availability, low cost, and diverse pharmacological activities, have increasingly gained attention. Various natural products, including polyphenols, flavonoids, terpenoids, and alkaloids, can target the RCD pathways involved in ADR-induced cardiotoxicity. Furthermore, these natural products have exhibited excellent properties in preclinical studies or in vitro experiments. This review summarizes the mechanisms of RCD in ADR-induced cardiotoxicity and systematically reviews the natural products targeting these RCD pathways. Finally, we propose future research directions of natural products in this field.
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series Cell Death Discovery
spelling doaj-art-9bf36c5b3201414a959b7c85a9f6906f2025-08-20T02:51:24ZengNature Publishing GroupCell Death Discovery2058-77162025-03-0111111510.1038/s41420-025-02389-wNatural products targeting regulated cell deaths for adriamycin-induced cardiotoxicityZheng Wang0Yanli Zhu1Yu Yao2Wenyu Zhang3Bo Wang4Jing Wang5Yang Yang6Liwen Liu7Xijing Hypertrophic Cardiomyopathy Center, Department of Ultrasound, Xijing Hospital, The Fourth Military Medical UniversityXi’an Key Laboratory of Innovative Drug Research for Heart Failure, Northwest University First Hospital, Faculty of Life Sciences and Medicine, Northwest UniversityXi’an Key Laboratory of Innovative Drug Research for Heart Failure, Northwest University First Hospital, Faculty of Life Sciences and Medicine, Northwest UniversityXi’an Key Laboratory of Innovative Drug Research for Heart Failure, Northwest University First Hospital, Faculty of Life Sciences and Medicine, Northwest UniversityXijing Hypertrophic Cardiomyopathy Center, Department of Ultrasound, Xijing Hospital, The Fourth Military Medical UniversityXijing Hypertrophic Cardiomyopathy Center, Department of Ultrasound, Xijing Hospital, The Fourth Military Medical UniversityXi’an Key Laboratory of Innovative Drug Research for Heart Failure, Northwest University First Hospital, Faculty of Life Sciences and Medicine, Northwest UniversityXijing Hypertrophic Cardiomyopathy Center, Department of Ultrasound, Xijing Hospital, The Fourth Military Medical UniversityAbstract Adriamycin (ADR), as an anti-cancer drug in routine clinical application, is utilized to treat various cancers such as ovarian cancer, hematological malignant tumor, and endometrial carcinoma. However, its serious dose-dependent cardiotoxicity extremely limits its clinical application. Currently, there remains a dearth of therapeutic agents to mitigate ADR-induced cardiotoxicity. Extensive research has demonstrated that ADR can simultaneously trigger various regulated cell death (RCD) pathways, such as apoptosis, autophagy, ferroptosis, necroptosis, and pyroptosis. Therefore, drugs targeting these RCD pathways may represent effective strategies for treating ADR-induced cardiotoxicity. Natural products, with their wide availability, low cost, and diverse pharmacological activities, have increasingly gained attention. Various natural products, including polyphenols, flavonoids, terpenoids, and alkaloids, can target the RCD pathways involved in ADR-induced cardiotoxicity. Furthermore, these natural products have exhibited excellent properties in preclinical studies or in vitro experiments. This review summarizes the mechanisms of RCD in ADR-induced cardiotoxicity and systematically reviews the natural products targeting these RCD pathways. Finally, we propose future research directions of natural products in this field.https://doi.org/10.1038/s41420-025-02389-w
spellingShingle Zheng Wang
Yanli Zhu
Yu Yao
Wenyu Zhang
Bo Wang
Jing Wang
Yang Yang
Liwen Liu
Natural products targeting regulated cell deaths for adriamycin-induced cardiotoxicity
Cell Death Discovery
title Natural products targeting regulated cell deaths for adriamycin-induced cardiotoxicity
title_full Natural products targeting regulated cell deaths for adriamycin-induced cardiotoxicity
title_fullStr Natural products targeting regulated cell deaths for adriamycin-induced cardiotoxicity
title_full_unstemmed Natural products targeting regulated cell deaths for adriamycin-induced cardiotoxicity
title_short Natural products targeting regulated cell deaths for adriamycin-induced cardiotoxicity
title_sort natural products targeting regulated cell deaths for adriamycin induced cardiotoxicity
url https://doi.org/10.1038/s41420-025-02389-w
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