Ring-fused chlorin-enhanced photodynamic therapy for effective cell death induction in endometrial cancer
The effectiveness of photodynamic therapy based on stable 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine-fused chlorins (PX) was explored in endometrial cancer. In vitro, photocytotoxicity of three derivatives of ring-fused chlorins (dihydroxymethyl, dicarboxylic acid, and dimethyl ester moieties) was evaluated in three endometrial cancer cell lines, ECC-1, RL95-2, and HEC-1-A. A comprehensive assessment of chlorins-induced intracellular production of reactive oxygen species, viability and PDT-induced types of cell death, influence on the cell cycle, intracellular localisation, and the protein expression of aldehyde dehydrogenase after photodynamic treatment was carried out. The photodynamic effect of the dihydroxymethyl derivative was then evaluated in vivo by monitoring tumour volume and performing histological and immunohistochemical analyses of the tumours. The dihydroxymethyl and dicarboxylic acid derivatives were the most active photosensitisers, presenting IC