OST-01, a natural product from Baccharis coridifolia, targets c-Myc-dependent ribogenesis in acute myeloid leukemia

作者：HyunJun Kang, Dinh Hoa Hoang, Melissa Valerio, Khyatiben V. Pathak, Lianjun Zhang, Ralf Buettner, Fang Chen, Katrina Estrella, William Graff, Zhuo Li, Jun Xie, David Horne, Ya‐Huei Kuo, Bin Zhang, Patrick Pirrotte, Le Xuan Truong Nguyen, Guido Marcucci · 发表于：Leukemia · 年份：2024 · DOI：10.1038/s41375-024-02146-5 · 被引用次数：4 · 研究领域：Sesquiterpenes and Asteraceae Studies、Natural Compounds in Disease Treatment、Bioactive Compounds and Antitumor Agents

Treatment refractoriness and post-remission relapse in patients with acute myeloid leukemia (AML) are often due to the persistence of leukemia stem cells (LSCs) [ 1 ], suggesting more effective and less toxic therapies targeting LSCs are highly needed for AML patients. Natural products (NP) played a role in drug discovery [ 2 , 3 ] and have been used in traditional medicine to treat a variety of conditions, including cancers [ 2 , 4 ]. South America, with its rich flora, harbors a variety of herbs used in healing remedies and more recently in phytomedicine. Baccharis coridifolia [ 5 ] (also known in Uruguay as “mío-mío”) has been long known as a poisonous plant affecting livestock in Uruguay [ 6 ]. Herein, we first report on antileukemic activity of OST-01, a novel NP extracted from Baccharis coridifolia , on AML “bulk” and LSC-enriched blasts. While the OST-01 mechanism of action (MOA) is likely multifaceted given the plethora of diverse molecular species generally contained in NPs, we observed that disruption of c-Myc-dependent ribosome biogenesis appears to be central to its antileukemic activity. OST-01 treatment on dose dependent for 24 h significantly inhibits proliferation and colony formation and induces apoptosis in representative AML cell lines (MV-4-11, KG-1a, Kasumi-1 and HL-60), primary CD34 + CD38- blasts (enriched for LSCs; see Table S1 for molecular features), but not normal CD34 + CD38- mononuclear cells (MNCs) [enriched for hematopoietic stem cells (HSC)] (F...