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A Cyclometalated Ir-III Complex Conjugated to a Coumarin Derivative Is a Potent Photodynamic Agent against Prostate Differentiated and Tumorigenic Cancer Stem Cells
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SYSNO ASEP 0542792 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název A Cyclometalated Ir-III Complex Conjugated to a Coumarin Derivative Is a Potent Photodynamic Agent against Prostate Differentiated and Tumorigenic Cancer Stem Cells Tvůrce(i) Novohradský, Vojtěch (BFU-R) ORCID
Marková, Lenka (BFU-R) ORCID
Kostrhunová, Hana (BFU-R) RID, ORCID
Kašpárková, Jana (BFU-R) RID, ORCID
Ruiz, J. (ES)
Marchan, V. (ES)
Brabec, Viktor (BFU-R) RID, ORCIDCelkový počet autorů 7 Zdroj.dok. Chemistry - A European Journal. - : Wiley - ISSN 0947-6539
Roč. 27, č. 33 (2021), s. 8547-8556Poč.str. 11 s. Forma vydání Tištěná - P Jazyk dok. eng - angličtina Země vyd. DE - Německo Klíč. slova calcium signals ; apoptosis ; antitumor agents ; apoptosis ; cancer stem cells Vědní obor RIV CE - Biochemie Obor OECD Physical chemistry CEP GA21-27514S GA ČR - Grantová agentura ČR Způsob publikování Open access Institucionální podpora BFU-R - RVO:68081707 UT WOS 000650224100001 EID SCOPUS 85105752243 DOI 10.1002/chem.202100568 Anotace A cyclometalated Ir-III complex conjugated to a far-red-emitting coumarin, Ir-III-COUPY (3), was recently shown as a very promising photosensitizer suitable for photodynamic therapy of cancer. Therefore, the primary goal of this work was to deepen knowledge on the mechanism of its photoactivated antitumor action so that this information could be used to propose a new class of compounds as drug candidates for curing very hardly treatable human tumors, such as androgen resistant prostatic tumors of metastatic origin. 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 conjugate 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 Ir-III-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 tumor spheres, which might markedly increase its therapeutic effect. Also interestingly, 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 CSCs. Pracoviště Biofyzikální ústav Kontakt Jana Poláková, polakova@ibp.cz, Tel.: 541 517 244 Rok sběru 2022 Elektronická adresa https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/chem.202100568
Počet záznamů: 1