biostudies-literatureUnknown28(2)Wang XA series of seven novel iridium complexes were synthetized and characterized as potential photosensitizers for photodynamic therapy (PDT) applications. Among them, four complexes were evaluated in vitro for their anti-proliferative activity with and without irradiation on a panel of five cancer cell lines, namely PC-3 (prostate cancer), T24 (bladder cancer), MCF7 (breast cancer), A549 (lung cancer) and HeLa (cervix cancer), and two non-cancerous cell models (NIH-3T3 fibroblasts and MC3T3 osteoblasts). After irradiation at 458 nm, all tested complexes showed a strong selectivity against cancer cells, with a selectivity index (SI) ranging from 8 to 34 compared with non-cancerous cells. The cytotoxic effect of all these complexes was found to be independent of the anti-apoptotic protein Bcl-xL. The compound exhibiting the best selectivity, complex <b>4a</b>, was selected for further investigations. Complex <b>4a</b> was mainly localized in the mitochondria. We found that the loss of cell viability and the decrease in ATP and GSH content induced by complex <b>4a</b> were independent of both Bcl-xL and caspase activation, leading to a non-apoptotic cell death. By counteracting the intrinsic or acquired resistance to apoptosis associated with cancer, complex <b>4a</b> could be an interesting therapeutic alternative to be studied in preclinical models.Molecules (Basel, Switzerland)691https://www.ebi.ac.uk/biostudies/studies/S-EPMC9861386biostudies-literature<i>N</i>-Heterocyclic Carbene-Iridium Complexes as Photosensitizers for In Vitro Photodynamic Therapy to Trigger Non-Apoptotic Cell Death in Cancer Cells.PMC9861386Deraeve CGornitzka HBijani CCuvillier OMadji RWang XMazeres SZhang CVoros CMaddelein MLHemmert Cfalse<i>N</i>-Heterocyclic Carbene-Iridium Complexes as Photosensitizers for In Vitro Photodynamic Therapy to Trigger Non-Apoptotic Cell Death in Cancer Cells.A series of seven novel iridium complexes were synthetized and characterized as potential photosensitizers for photodynamic therapy (PDT) applications. Among them, four complexes were evaluated in vitro for their anti-proliferative activity with and without irradiation on a panel of five cancer cell lines, namely PC-3 (prostate cancer), T24 (bladder cancer), MCF7 (breast cancer), A549 (lung cancer) and HeLa (cervix cancer), and two non-cancerous cell models (NIH-3T3 fibroblasts and MC3T3 osteoblasts). After irradiation at 458 nm, all tested complexes showed a strong selectivity against cancer cells, with a selectivity index (SI) ranging from 8 to 34 compared with non-cancerous cells. The cytotoxic effect of all these complexes was found to be independent of the anti-apoptotic protein Bcl-xL. The compound exhibiting the best selectivity, complex <b>4a</b>, was selected for further investigations. Complex <b>4a</b> was mainly localized in the mitochondria. We found that the loss of cell viability and the decrease in ATP and GSH content induced by complex <b>4a</b> were independent of both Bcl-xL and caspase activation, leading to a non-apoptotic cell death. By counteracting the intrinsic or acquired resistance to apoptosis associated with cancer, complex <b>4a</b> could be an interesting therapeutic alternative to be studied in preclinical models.2023-01-01T00:00:00Z2023 Jan2025-04-04T11:33:32.597Z2025-04-04T11:33:32.597ZS-EPMC98613863667775110.3390/molecules28020691