Yang Yingying, Spagnuolo Paul A
Department of Food Science, University of Guelph, Guelph, Canada.
Front Pharmacol. 2025 Jun 24;16:1621050. doi: 10.3389/fphar.2025.1621050. eCollection 2025.
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.
We conducted a natural compound library screen and identified 6-methoxydihydroavicine, a plant-derived benzophenanthridine alkaloid (BPA) derived from the genus of - 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.
6-methoxydihydroavicine significantly reduced cell viability and induced caspase-mediated cell death in AML cell lines in a dose-dependent manner. Mechanistically, 6-methoxydihydroavicine triggered accumulation of mitochondrial ROS and disrupted electron transport chain (ETC) function.
Our findings demonstrate that 6-methoxydihydroavicine exerts strong cytotoxic effects against AML cells through mitochondrial dysfunction and ROS-mediated apoptosis. As a natural, plant-derived compound with distinct anti-AML properties, 6-methoxydihydroavicine represents a promising candidate for further development as a therapeutic agent for AML.
急性髓系白血病（AML）是一种侵袭性血液系统恶性肿瘤，治疗选择有限。尽管靶向治疗最近取得了进展，但患者的生存结果仍然很差。因此，开发具有广泛疗效的新型治疗药物仍然是一项迫切需求。
我们进行了天然化合物库筛选，鉴定出6-甲氧基二氢阿维辛，一种源自中国、北美和欧洲的多年生草本植物属的植物源性苯并菲啶生物碱（BPA），作为一种能降低AML细胞活力的有效化合物。我们评估了其在多种AML细胞系中的细胞毒性，并使用探测线粒体功能和活性氧（ROS）产生的试验研究了其潜在的作用机制。
6-甲氧基二氢阿维辛以剂量依赖的方式显著降低AML细胞系中的细胞活力并诱导半胱天冬酶介导的细胞死亡。从机制上讲，6-甲氧基二氢阿维辛引发线粒体ROS的积累并破坏电子传递链（ETC）功能。
我们的研究结果表明，6-甲氧基二氢阿维辛通过线粒体功能障碍和ROS介导的凋亡对AML细胞发挥强大的细胞毒性作用。作为一种具有独特抗AML特性的天然植物源性化合物，6-甲氧基二氢阿维辛代表了一种有前途的候选药物，可进一步开发为AML的治疗药物。
