Galanthamine Fails to Reverse P-gp-Mediated Paclitaxel Resistance in Ovarian Cancer Cell Lines

<b>Background</b>: Ovarian cancer has the poorest prognosis of all gynecological malignancies, largely due to its chemoresistance, which poses significant treatment challenges. In this context, drug repurposing emerges as an innovative strategy that employs non-cancer treatments to interact with various signaling pathways, enhancing chemotherapy efficacy while minimizing toxicity. This study investigated the cytotoxic effects of galanthamine, currently used as an Alzheimer's disease, as a potential treatment for high-grade serous carcinoma, both individually and in combination with paclitaxel. <b>Methods:</b> The Presto Blue assay, viability marker assessments, immunocytochemical analysis of apoptosis, and a cumulative assay were employed to evaluate the functionality of P-glycoprotein. <b>Results:</b> The results indicated that galanthamine did not demonstrate cytotoxic or synergistic effects in either high-grade serous carcinoma cell line tested, suggesting that it is not a viable strategy for overcoming paclitaxel resistance in this context. The immunocytochemistry analysis indicated that galanthamine does not affect the expression of proteins related to cell viability and proliferation and is not associated with chemoresistance. Additionally, functional assays showed that galanthamine treatment did not affect its drug efflux function at the cellular level. <b>Conclusions:</b> Overall, the results indicate that galanthamine is unsuitable for reversing paclitaxel resistance despite some literature suggesting its potential interaction with P-glycoprotein.