NATURAL ALKALOID BOLDINE REDUCES PROLIFERATION IN GLIOBLASTOMA CELL LINES AND PRIMARY HUMAN CULTURES

Glioblastoma (GBM) is the most aggressive primary brain tumor, with limited therapeutic options and frequent resistance to temozolomide (TMZ). Boldine, a natural alkaloid derived from Peumus boldus, has shown antiproliferative and pro-apoptotic properties in different cancer cell lines. This study aimed to evaluate the antiproliferative effects of boldine on different GBM cellular models and to assess its potential synergistic action with TMZ. Human GBM cell lines (U87‑MG, T98G, GBM59, GBM96), a murine GBM line (GL261), and a primary culture derived from human GBM were treated with increasing concentrations of boldine (25–600 μM) for 72 h. Cell viability was assessed by MTT assays, and dose–response curves were generated to calculate IC₅₀ values. Cellular proliferation in primary GBM cultures was evaluated by bromodeoxyuridine (BrdU) incorporation and the percentage of apoptotic cells by the TUNEL technique. Boldine induced a significant, dose‑dependent reduction in cell viability across all GBM cell lines, with IC₅₀ values ranging from 68.6 to 213.8 μM, without increasing apoptosis. In primary GBM cultures, boldine markedly reduced BrdU incorporation. Boldine showed a stronger antiproliferative effect than TMZ in several GBM lines and its combination with TMZ did not produce additional benefits. These findings demonstrate that boldine exerts robust antiproliferative effects in different GBM cells, greater than those produced by TMZ. Boldine emerges as a promising therapeutic candidate for GBM, warranting further preclinical studies to elucidate its mechanisms of action and translational potential.
Acknowledgements: EU-Ministerio de Hacienda y Función Pública-European Funds-Junta de Andalucía for RGB predoctoral contract.