Goetzfried Sina Katharina, Hakkennes Matthijs L A, Busemann Anja, Bonnet Sylvestre
Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333CC Leiden, The Netherlands.
ACS Pharmacol Transl Sci. 2025 Jan 30;8(2):484-498. doi: 10.1021/acsptsci.4c00600. eCollection 2025 Feb 14.
Glioblastoma multiforme (GBM) is highly aggressive, necessitating new therapies. Photoactivated chemotherapy (PACT) offers a promising approach by activating prodrugs with visible light at the tumor site. This study evaluated the anticancer activity of ruthenium-based PACT compounds in U-87MG glioblastoma cells and their safety in SH-SY5Y neuron-like cells. The compound showed promising light-activated anticancer effects in U-87MG cells, while was inactive, and was nonactivated. Interestingly, in SH-SY5Y cells, light-activated increased cell proliferation, similar to donepezil, without causing cell death. Increased Ca uptake was observed, possibly via interaction with the AMPA receptor, as suggested by docking studies. These findings suggest ruthenium-based PACT compounds may serve as potential treatments for GBM, effectively attacking cancer cells while preserving healthy neuronal cells.