Plant Extracts from Origanum vulgare and Vaccinium macrocarpon Induce Apoptosis of Bone Metastasized Breast Cancer Cells in a 3D Bone-Mimetic Testbed of Bone Metastasis

Bone metastasis remains a fatal and incurable condition for patients with breast cancer, leading to skeletal deterioration. The bone microenvironment enhances tumor proliferation and chemoresistance, necessitating novel therapeutic strategies. To investigate the cytotoxicity of two phytochemically-enriched plant extracts: <i>Origanum vulgare</i> (O.V.) and <i>Vaccinium macrocarpon</i> (V.M.) against breast cancer cells in a bone-metastatic condition. MCF-7 and MDA-MB-231 cell lines were treated with O.V. and V.M. for 24 h, in both 2D and 3D bone metastatic conditions. Live cell imaging, Alamar blue viability assay, RT-PCR, and flow cytometry analysis were used to assess cytotoxicity, apoptosis activation, and changes in oxidative stress/mitochondrial activity. Both extracts significantly inhibited cancer cell growth in a dose-dependent manner, with differential sensitivity observed between cell lines. Based on IC50 analysis, O.V. demonstrated greater efficacy against the bone metastatic MCF-7 cell line, while V.M. was more effective against the bone metastatic MDA-MB-231. Apoptosis activation was confirmed via upregulation of pro-apoptotic proteins p53 and caspase-9. Importantly, we observed that normal bone cells were unaffected by the treatments. These findings elucidate the promising yet untapped potential of O.V. and V.M. extracts as robust therapies for bone metastasis.