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
Department of Hematologic Malignancies Translational Science, Beckman Research Institute and City of Hope National Medical Center, Duarte, CA, USA.
Early Detection and Prevention Division, Translational Genomics Research Institute, Phoenix, AZ, USA.
J Hematol Oncol. 2025 Feb 7;18(1):16. 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.
天然产物长期以来一直是治疗药物的可行来源，提供可能有益于癌症治疗的独特结构和机制。在此，我们首次报道了来自羽叶酒神菊的天然产物OST-01对乳腺癌细胞，包括三阴性乳腺癌（TNBC）的抗癌活性。OST-01在体外显著抑制TNBC细胞的增殖和致癌活性。在不同的体内模型，即细胞系衍生（CDX）、患者衍生（PDX）和乳腺脂肪垫异种移植模型中，OST-01还显著抑制TNBC肿瘤的生长，与载体对照处理相比，肿瘤大小减少超过50%。从机制上讲，OST-01通过下调LRP8调节的硒蛋白，即GPX4来诱导铁死亡。还观察到乳腺癌干细胞（BCSCs）从基底间充质向管腔上皮的转变，这由干性（如CD44）和间充质（如FN1和波形蛋白）标志物的下调以及分化标志物（如CD24）和管腔上皮标志物（如CK19）的上调所支持。
