ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Ethnopharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1621050
This article is part of the Research TopicMedicinal Plants from the Americas: A Source of Biologically Active Extracts and MetabolitesView all 5 articles
6-Methoxydihydroavicine is a benzophenanthridine alkaloid with anti-leukemia activity
Provisionally accepted
- University of Guelph, Guelph, Canada
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Background: Acute myeloid leukemia (AML) is an aggressive hematological malignancy with limited therapeutic options. Despite recent advances in targeted therapies, patients are still faced with poor survival outcomes. Thus, development of novel therapeutic agents with broad efficacy remains an urgent need.Methods: We conducted a natural compound library screen and identified 6methoxydihydroavicine (6ME), a plant-derived benzophenanthridine alkaloid (BPA) derived from the genus of Macleaya -a perennial herb found in China, North America and Europe -as a potent compound that reduced AML cell viability. We evaluated its cytotoxicity in multiple AML cell lines and investigated its underlying mechanism of action using assays that probed mitochondrial function, and reactive oxygen species (ROS) production.Results: 6ME6-methoxydihydroavicine significantly reduced cell viability and induced caspasemediated cell death in AML cell lines in a dose-dependent manner. Mechanistically, 6ME6methoxydihydroavicine triggered accumulation of mitochondrial ROS and disrupted electron transport chain (ETC) function.Our findings demonstrate that 6ME6-methoxydihydroavicine exerts strong cytotoxic effects against AML cells through mitochondrial dysfunction and ROS-mediated apoptosis. As a novel natural, plant-derived compound with distinct anti-AML properties, 6ME6methoxydihydroavicine represents a promising candidate for further development as a therapeutic agent for AML.
Keywords: Benzophenanthridine alkaloid, 6-methoxydihydroavicine, Acute Myeloid Leukemia, ROS, Metabolism
Received: 30 Apr 2025; Accepted: 09 Jun 2025.
Copyright: © 2025 Yang and Spagnuolo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Paul Spagnuolo, University of Guelph, Guelph, Canada
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