Pharmacological activity of OST-01, a natural product from baccharis coridifolia, on breast cancer cells

• Published in: Journal of hematology and oncology Vol. 18; no. 1; pp. 16 - 6
• Main Authors: Kang, HyunJun, Hoang, Dinh Hoa, Valerio, Melissa, Pathak, Khyatiben, Graff, William, LeVee, Alexis, Wu, Jun, LaBarge, Mark A., Frankhouser, David, Rockne, Russell C., Pirrotte, Patrick, Zhang, Bin, Mortimer, Joanne, Nguyen, Le Xuan Truong, Marcucci, Guido
• Format: Journal Article
• Language: English
• Published: London BioMed Central 07.02.2025; BioMed Central Ltd; BMC
• Subjects: Animals; Antineoplastic Agents, Phytogenic - pharmacology; Antitumor activity; Apoptosis; BCSC; Biological Products - pharmacology; Biological Products - therapeutic use; Breast cancer; Cancer; Cancer cells; Cancer Research; Cancer therapies; Care and treatment; CD44 antigen; Cell culture; Cell cycle; Cell death; Cell Line, Tumor; Cell proliferation; Cell Proliferation - drug effects; Comparative analysis; Correspondence; Female; Ferroptosis; Ferroptosis - drug effects; Genes; Health aspects; Hematology; Humans; Leukemia; Lipid peroxidation; Medicine; Medicine & Public Health; Metabolism; Mice; Natural product; Natural products; Neoplastic Stem Cells - drug effects; Neoplastic Stem Cells - pathology; Oncology; OST-01; Oxidative stress; Selenoproteins; Stem cells; TNBC; Toxicity; Triple Negative Breast Neoplasms - drug therapy; Triple Negative Breast Neoplasms - pathology; Tumors; Vimentin; Xenograft Model Antitumor Assays; Natural product; OST-01; Ferroptosis; TNBC; BCSC
• ISSN: 1756-8722; 1756-8722
• DOI: 10.1186/s13045-025-01668-4

Natural products have long been a viable source of therapeutic agents, providing unique structures and mechanisms that may be beneficial for cancer treatment. Herein we first report on the anticancer activity OST-01, a natural product from Baccharis Coridifolia, on breast cancer cells, including triple-negative breast cancer (TNBC). OST-01 significantly inhibited cell proliferation and oncogenic activities of TNBC cells in vitro. OST-01 also markedly inhibited TNBC tumor growth in vivo, with > 50% reduction in tumor size compared to vehicle control treatment in different in vivo models, i.e., cell line-derived (CDX), patient-derived (PDX), and mammary fat pad xenografts. Mechanistically, OST-01 induces ferroptosis by downregulating LRP8-regulated selenoproteins, i.e., GPX4. A shift from a basal-mesenchymal to a luminal-epithelial state of breast cancer stem cells (BCSCs) as supported by the downregulation of stemness (e.g., CD44) and mesenchymal (e.g., FN1 and vimentin) markers, along with the upregulation of differentiation markers (e.g., CD24) and luminal-epithelial markers (e.g., CK19), was also observed.