Machine learning-powered discovery of a novel berberine derivative inducing SCD-dependent ferroptosis in osteosarcoma.

ABSTRACT:

Background

Despite decades of therapeutic development, osteosarcoma survival remains poor. Although berberine (BBR) shows anti-tumor activity, its efficacy is limited. We addressed this through structural modification and machine learning-guided discovery, developing a novel derivative: 9-O-methoxyethylberberrubine bromide (B1).

Methods

In vivo, subcutaneous and orthotopic models were established in BALB/c nude mice using 143B cells. Treatment groups received daily B1 (0.1-5 mg/kg) or berberine (5, 50 mg/kg); a positive control group received doxorubicin (1 mg/kg). Tumor growth was assessed by volume and weight; tissue necrosis, proliferation, and apoptosis were analyzed. In vitro, human osteosarcoma cells (143B, U2OS, HOS) and human bone marrow mesenchymal stem cells (hBMSC

SUBMITTER: He M 

PROVIDER: S-EPMC12636167 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature