TY - JOUR TI - A Cyclometalated IrIII Complex Conjugated to a Coumarin Derivative Is a Potent Photodynamic Agent against Prostate Differentiated and Tumorigenic Cancer Stem Cells AU - Novohradsky, Vojtech AU - Markova, Lenka AU - Kostrhunova, Hana AU - Kasparkova, Jana AU - Ruiz, José AU - Marchán, Vicente AU - Brabec, Viktor T2 - Chemistry – A European Journal AB - A cyclometalated IrIII complex conjugated to a far-red-emitting coumarin, IrIII–COUPY (3), was recently shown as a very promising photosensitizer suitable for photodynamic therapy of cancer. Conventional anticancer chemotherapies exhibit several disadvantages, such as limited efficiency to target cancer stem cells (CSCs), which are considered the main reason for chemotherapy resistance, relapse, and metastasis. Herein, we show, using DU145 tumor cells, taken as the model of hormone-refractory and aggressive prostate cancer cells resistant to conventional antineoplastic drugs, that the photoactivated 3 very efficiently eliminates both prostate bulk, differentiated and prostate, hardly treatable CSCs simultaneously and with a similar efficiency. Notably, the very low toxicity of IrIII–COUPY conjugate in the prostate DU145 cells in the dark and its pronounced selectivity for tumor cells compared with noncancerous cells could result in low side effects and reduced damage of healthy cells during the photoactivated therapy by this agent. Moreover, the experiments performed with the 3D spheroids formed from DU145 CSCs showed that conjugate 3 can penetrate the inner layers of tumorspheres, which might markedly increase its therapeutic effect. Notably, this conjugate induces apoptotic cell death in prostate cancer DU145 cells associated with calcium signaling flux in these cells and autophagy. To the best of our knowledge, this is the first study demonstrating that a photoactivatable metal-based compound is an efficient agent capable of killing even hardly treatable prostatic CSCs. DO - https://doi.org/10.1002/chem.202100568 DP - Wiley Online Library VL - n/a IS - n/a LA - en SN - 1521-3765 UR - https://chemistry-europe.onlinelibrary.wiley.com/doi/abs/10.1002/chem.202100568 Y2 - 2021/04/15/22:49:50 KW - Iridium KW - Prostate cancer KW - antitumor agents KW - cancer stem cells KW - coumarin photoactivation ER -