Natural products targeting regulated cell deaths for adriamycin-induced cardiotoxicity
Zheng Wang1,2, Yanli Zhu3, Yu Yao3
1Xijing Hypertrophic Cardiomyopathy Center, Department of Ultrasound, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an, 710032, China.
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.
Insights
Adriamycin (ADR) causes heart damage by triggering cell death pathways. Natural products show promise in protecting against this cardiotoxicity by targeting these pathways.
Area of Science:
- Cardiology
- Pharmacology
- Oncology
Background:
- Adriamycin (ADR) is a vital anti-cancer drug but causes dose-dependent cardiotoxicity, limiting its use.
- Current treatments for ADR-induced cardiotoxicity are insufficient.
- ADR induces multiple regulated cell death (RCD) pathways, including apoptosis, autophagy, ferroptosis, necroptosis, and pyroptosis.
Purpose of the Study:
- To review the mechanisms of RCD in ADR-induced cardiotoxicity.
- To systematically examine natural products that target RCD pathways implicated in ADR cardiotoxicity.
- To propose future research directions for natural products in mitigating ADR cardiotoxicity.
Main Methods:
- Literature review focusing on RCD mechanisms in ADR cardiotoxicity.
- Systematic search and analysis of natural products targeting these RCD pathways.
- Evaluation of preclinical and in vitro data on natural product efficacy.
Main Results:
- ADR triggers diverse RCD pathways contributing to cardiotoxicity.
- Natural products (polyphenols, flavonoids, terpenoids, alkaloids) demonstrate potential in targeting these RCD pathways.
- Preclinical and in vitro studies support the efficacy of various natural products.
Conclusions:
- Targeting RCD pathways is a viable strategy for managing ADR-induced cardiotoxicity.
- Natural products offer a promising avenue for developing novel therapeutic agents.
- Further research into natural products for ADR cardiotoxicity is warranted.
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