@article{article_1639903, title={Cytotoxic and Metastatic Effects of Anatolian Propolis and Chemotherapeutic Agents (DOX, TAM, CLB) in 2D and 3D Breast Cancer Models}, journal={Journal of Apitherapy and Nature}, volume={8}, pages={103–127}, year={2025}, DOI={10.35206/jan.1639903}, author={Arslan, Habibe Sema and Yalçın Azarkan, Serap and Turna Saltoğlu, Gamze}, keywords={Propolis, Doksorubisin, Tamoksifen, Klorambusil, MDA-MB-231}, abstract={This study aims to comparatively investigate the cytotoxic and metastatic effects of Anatolian propolis and chemotherapeutic agents (Doxorubicin- DOX, Tamoxifen- TAM, Chlorambucil- CLB) on two-dimensional (2D) and three-dimensional (3D) breast cancer cell cultures. The triple-negative MDA-MB-231 breast cancer cell line was cultured in 2D and 3D models. Anatolian propolis was prepared using ethanol extraction and applied to the cells alone or in combination with chemotherapeutic agents (DOX, TAM, CLB) at their respective IC50 doses. Cytotoxicity was assessed using the XTT assay, while cell migration and invasion were evaluated using wound healing and invasion assays. Propolis, when combined with chemotherapeutic agents, significantly inhibited cell proliferation and migration (p <0.001). TAM alone exhibited an IC50 value of 0.5 µM, whereas TAM + Propolis (40 mg/mL) more effectively suppressed proliferation and migration (p <0.001). For CLB applications, the IC50 value was determined as 10 µM, and CLB+Propolis (40 mg/mL) reduced cell viability while suppressing metastatic activity (p <0.001). In 3D cultures, CLB+Propolis (80 mg/mL) disrupted spheroid integrity, preventing cancer cell dissemination (p <0.01). DOX exhibited an IC50 value of 5 µM, and DOX+Propolis (40 mg/mL) increased cell death (p <0.001). In 3D cultures, DOX+Propolis (80 mg/mL) further inhibited cell invasion by breaking down spheroid structures (p <0.001). Across all combination groups, propolis enhanced the efficacy of chemotherapeutic agents and significantly suppressed cell migration and invasion (p <0.001). The pronounced effects observed in 3D cultures suggest that propolis may act as a potent anti-metastatic agent within the tumor microenvironment. These findings indicate that propolis may serve as a complementary agent to enhance chemotherapy sensitivity; however, further preclinical and clinical studies are required to confirm its clinical applicability.}, number={1}, publisher={Oktay YILDIZ}, organization={Kırsehir Ahi Evran University Scientific Research Projects Coordination Unit}