Evaluating the Anticancer and Anti-Angiogenic Efficacy of Bergaptol in 2D and 3D Tumor Microtissue Models

Furanocoumarins are plant-derived compounds with diverse biological activities and emerging therapeutic potential. This study evaluated the anticancer and anti-angiogenic properties of bergaptol by using MDA-MB-231, HepG2, and HeLa cancer cell lines, as well as HUVEC endothelial cells, with HDFs serving as the healthy control group. Cell viability, apoptosis, cell-cycle progression, and angiogenesis were evaluated using complementary two-dimensional (2D) and three-dimensional (3D) experimental models. Bergaptol exhibited selective cytotoxicity toward cancer and endothelial cells, with no apparent cytotoxicity toward HDFs. Treatment induced apoptosis, disrupted cell-cycle progression, and suppressed angiogenic activity. In 3D models, bergaptol reduced spheroid viability, diminished spheroid size, and decreased endothelial cell content. An ex vivo assay, the chorioallantoic membrane (CAM) assay, corroborated these observations, demonstrated a substantial inhibition of neovascularization, and further supports its anti-angiogenic potential. These findings demonstrate that bergaptol exhibits both anticancer and anti-angiogenic activity in 2D and 3D experimental models supporting further evaluation of bergaptol as a potential anticancer agent.