A brachydin-rich fraction from Fridericia platyphylla induces apoptosis in breast cancer cells via upregulation of AIFM1 and BAX and reduced tumor growth in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: Fridericia platyphylla (Cham.) L.G. Lohmann is traditionally used in Brazilian folk medicine to treat kidney stones, inflammatory disorders, and cancer. Previous studies demonstrated that its major dimeric flavonoids, the brachydins, exhibit diverse biological activities, including antitumor effects. AIM OF THE STUDY: To evaluate the antitumor potential of a brachydin-rich dichloromethane fraction (DCMF) obtained from F. platyphylla roots. MATERIALS AND METHODS: DCMF was obtained by partitioning the water/methanol-solubilized crude extract into dichloromethane, and the extract was analyzed by HPLC. In 2D, MCF-7 cells were treated with DCMF and evaluated for cytotoxicity, clonogenic potential, genotoxicity, cell death, and apoptosis-related gene expression. In spheroids, cytotoxicity, spheroid integrity, and extracellular matrix migration were assessed. The antitumor efficacy was evaluated in a syngeneic orthotopic model in which tumor-bearing mice received intratumoral DCMF at 5 or 10 mg/kg body weight every 72 h for 15 days. RESULTS: DCMF induced time-dependent cytotoxicity in MCF-7 cells, reduced clonogenic survival, increased DNA damage, and changes in AIFM1, BAX, and BCL-2 gene expression, supporting a caspase-independent apoptotic response. In the 3D model, DCMF impaired spheroid integrity and reduced cell migration, demonstrating activity in a more physiologically relevant tumor architecture. In vivo, intratumoral administration of DCMF (10 mg/kg) reduced tumor growth by 66.04% and decreased mitotic frequency, without evident systemic toxicity. CONCLUSIONS: The present findings demonstrate that DCMF retains antitumor activity beyond conventional 2D models, highlighting the preclinical potential of DCMF as a source of potential bioactive flavonoids for breast cancer research.