Ferroptosis: a novel pharmacological mechanism against multiple myeloma
BackgroundMultiple myeloma (MM) is a malignant disease characterized by the clonal proliferation of plasma cells in the bone marrow. Currently incurable, relapse and drug resistance remain significant challenges, necessitating the exploration of novel anti-MM agents. Ferroptosis, a form of cell deat...
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Frontiers Media S.A.
2025-07-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1606804/full |
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| author | Jingbo Shi Yitong Lu Wenjian Wei Guodong Ma Changnian Li Lulu Li Yaru Wang Yan Wang Ruirong Xu Siyuan Cui |
| author_facet | Jingbo Shi Yitong Lu Wenjian Wei Guodong Ma Changnian Li Lulu Li Yaru Wang Yan Wang Ruirong Xu Siyuan Cui |
| author_sort | Jingbo Shi |
| collection | DOAJ |
| description | BackgroundMultiple myeloma (MM) is a malignant disease characterized by the clonal proliferation of plasma cells in the bone marrow. Currently incurable, relapse and drug resistance remain significant challenges, necessitating the exploration of novel anti-MM agents. Ferroptosis, a form of cell death driven by iron-dependent lipid peroxidation, has emerged as a critical player in MM pathology and treatment. With advancing research, emerging evidence links ferroptosis to MM pathogenesis and therapeutic strategies. Natural products (NPs) and certain antitumor agents, owing to their broad bioactivities, demonstrate unique pharmacological advantages in MM therapy by targeting ferroptosis-related pathways.PurposeThis review systematically examines ferroptosis-related pathways in MM pathogenesis, focusing on pharmacological and toxicological mechanisms of natural products (NPs) and antitumor compounds in modulating ferroptosis-related pathways. It aims to provide novel insights and strategies for MM research and clinical therapy.MethodsWe systematically retrieved data from PubMed, Web of Science, ScienceDirect, SciFinder, Scopus, and the China National Knowledge Infrastructure (CNKI) spanning database inception to March 2025, followed by taxonomic integrative analysis of NPs’ and antitumor compounds’ echanistic classifications.ResultsNPs and antitumor compounds exert anti-MM effects via ferroptosis modulation, mechanistically mediated through: 1) lipid metabolism reprogramming; 2) ferritinophagy-driven iron homeostasis regulation; 3) Reactive oxygen species (ROS)-mediated oxidative stress potentiation; 4) autophagic activation; 5) Genes and proteins regulation.ConclusionNPs and antitumor compounds demonstrate therapeutic potential against MM through multi-dimensional ferroptosis modulation, yet clinical translation faces two critical hurdles: 1) predominant focus on single-target mechanisms lacking systems pharmacology-level network analysis; 2) overreliance on in vitro models with insufficient clinical validation. Prioritize developing biomarkers and ferroptosis inducers to advance novel ferroptosis-targeting anticancer compounds. |
| format | Article |
| id | doaj-art-aa5c0a0ea7f942e7bb571c11356b660c |
| institution | Kabale University |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-aa5c0a0ea7f942e7bb571c11356b660c2025-08-20T03:25:26ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-07-011610.3389/fphar.2025.16068041606804Ferroptosis: a novel pharmacological mechanism against multiple myelomaJingbo Shi0Yitong Lu1Wenjian Wei2Guodong Ma3Changnian Li4Lulu Li5Yaru Wang6Yan Wang7Ruirong Xu8Siyuan Cui9Department of First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, ChinaDepartment of First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, ChinaDepartment of First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, ChinaDepartment of First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, ChinaDepartment of First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, ChinaDepartment of First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, ChinaDepartment of First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, ChinaDepartment of Hematology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, ChinaDepartment of Hematology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, ChinaDepartment of Hematology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, ChinaBackgroundMultiple myeloma (MM) is a malignant disease characterized by the clonal proliferation of plasma cells in the bone marrow. Currently incurable, relapse and drug resistance remain significant challenges, necessitating the exploration of novel anti-MM agents. Ferroptosis, a form of cell death driven by iron-dependent lipid peroxidation, has emerged as a critical player in MM pathology and treatment. With advancing research, emerging evidence links ferroptosis to MM pathogenesis and therapeutic strategies. Natural products (NPs) and certain antitumor agents, owing to their broad bioactivities, demonstrate unique pharmacological advantages in MM therapy by targeting ferroptosis-related pathways.PurposeThis review systematically examines ferroptosis-related pathways in MM pathogenesis, focusing on pharmacological and toxicological mechanisms of natural products (NPs) and antitumor compounds in modulating ferroptosis-related pathways. It aims to provide novel insights and strategies for MM research and clinical therapy.MethodsWe systematically retrieved data from PubMed, Web of Science, ScienceDirect, SciFinder, Scopus, and the China National Knowledge Infrastructure (CNKI) spanning database inception to March 2025, followed by taxonomic integrative analysis of NPs’ and antitumor compounds’ echanistic classifications.ResultsNPs and antitumor compounds exert anti-MM effects via ferroptosis modulation, mechanistically mediated through: 1) lipid metabolism reprogramming; 2) ferritinophagy-driven iron homeostasis regulation; 3) Reactive oxygen species (ROS)-mediated oxidative stress potentiation; 4) autophagic activation; 5) Genes and proteins regulation.ConclusionNPs and antitumor compounds demonstrate therapeutic potential against MM through multi-dimensional ferroptosis modulation, yet clinical translation faces two critical hurdles: 1) predominant focus on single-target mechanisms lacking systems pharmacology-level network analysis; 2) overreliance on in vitro models with insufficient clinical validation. Prioritize developing biomarkers and ferroptosis inducers to advance novel ferroptosis-targeting anticancer compounds.https://www.frontiersin.org/articles/10.3389/fphar.2025.1606804/fullmultiple myelomaferroptosispharmacological mechanismnatural productsantitumor effects |
| spellingShingle | Jingbo Shi Yitong Lu Wenjian Wei Guodong Ma Changnian Li Lulu Li Yaru Wang Yan Wang Ruirong Xu Siyuan Cui Ferroptosis: a novel pharmacological mechanism against multiple myeloma Frontiers in Pharmacology multiple myeloma ferroptosis pharmacological mechanism natural products antitumor effects |
| title | Ferroptosis: a novel pharmacological mechanism against multiple myeloma |
| title_full | Ferroptosis: a novel pharmacological mechanism against multiple myeloma |
| title_fullStr | Ferroptosis: a novel pharmacological mechanism against multiple myeloma |
| title_full_unstemmed | Ferroptosis: a novel pharmacological mechanism against multiple myeloma |
| title_short | Ferroptosis: a novel pharmacological mechanism against multiple myeloma |
| title_sort | ferroptosis a novel pharmacological mechanism against multiple myeloma |
| topic | multiple myeloma ferroptosis pharmacological mechanism natural products antitumor effects |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1606804/full |
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