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An anticancer Os(II) bathophenanthroline complex as a human breast cancer stem cell-selective, mammosphere potent agent that kills cells by necroptosis

Conventional chemotherapy is mostly effective in the treatment of rapidly-dividing differentiated tumor cells but has limited application toward eliminating cancer stem cell (CSC) population. The presence of a very small number of CSCs may contribute to the development of therapeutic resistance, met...

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Autores principales: Novohradsky, Vojtech, Markova, Lenka, Kostrhunova, Hana, Trávníček, Zdeněk, Brabec, Viktor, Kasparkova, Jana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6746710/
https://www.ncbi.nlm.nih.gov/pubmed/31527683
http://dx.doi.org/10.1038/s41598-019-49774-x
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author Novohradsky, Vojtech
Markova, Lenka
Kostrhunova, Hana
Trávníček, Zdeněk
Brabec, Viktor
Kasparkova, Jana
author_facet Novohradsky, Vojtech
Markova, Lenka
Kostrhunova, Hana
Trávníček, Zdeněk
Brabec, Viktor
Kasparkova, Jana
author_sort Novohradsky, Vojtech
collection PubMed
description Conventional chemotherapy is mostly effective in the treatment of rapidly-dividing differentiated tumor cells but has limited application toward eliminating cancer stem cell (CSC) population. The presence of a very small number of CSCs may contribute to the development of therapeutic resistance, metastases, and relapse. Thus, treatment failure by developing novel anticancer drugs capable of effective targeting of CSCs is at present a major challenge for research focused on chemotherapy of cancer. Here, we show that Os(II) complex 2 [Os(η(6)-pcym)(bphen)(dca)]PF(6) (pcym = p-cymene, bphen = bathophenanthroline, and dca = dichloroacetate), is capable of efficient and selective killing CSCs in heterogeneous populations of human breast cancer cells MCF-7 and SKBR-3. Notably, its remarkable submicromolar potency to kill CSCs is considerably higher than that of its Ru analog, [Ru(η(6)-pcym)(bphen)(dca)]PF(6) (complex 1) and salinomycin, one of the most selective CSC-targeting compounds hitherto identified. Furthermore, Os(II) complex 2 reduces the formation, size, and viability of three-dimensional mammospheres which more closely reflect the tumor microenvironment than cells in traditional two-dimensional cultures. The antiproliferation studies and propidium iodide staining using flow cytometry suggest that Os(II) complex 2 induces human breast cancer stem cell death predominantly by necroptosis, a programmed form of necrosis. The results of this study demonstrate the promise of Os(II) complex 2 in treating human breast tumors. They also represent the foundation for further preclinical and clinical studies and applications of Os(II) complex 2 to comply with the emergent need for human breast CSCs-specific chemotherapeutics capable to treat chemotherapy-resistant and relapsed human breast tumors.
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spelling pubmed-67467102019-09-27 An anticancer Os(II) bathophenanthroline complex as a human breast cancer stem cell-selective, mammosphere potent agent that kills cells by necroptosis Novohradsky, Vojtech Markova, Lenka Kostrhunova, Hana Trávníček, Zdeněk Brabec, Viktor Kasparkova, Jana Sci Rep Article Conventional chemotherapy is mostly effective in the treatment of rapidly-dividing differentiated tumor cells but has limited application toward eliminating cancer stem cell (CSC) population. The presence of a very small number of CSCs may contribute to the development of therapeutic resistance, metastases, and relapse. Thus, treatment failure by developing novel anticancer drugs capable of effective targeting of CSCs is at present a major challenge for research focused on chemotherapy of cancer. Here, we show that Os(II) complex 2 [Os(η(6)-pcym)(bphen)(dca)]PF(6) (pcym = p-cymene, bphen = bathophenanthroline, and dca = dichloroacetate), is capable of efficient and selective killing CSCs in heterogeneous populations of human breast cancer cells MCF-7 and SKBR-3. Notably, its remarkable submicromolar potency to kill CSCs is considerably higher than that of its Ru analog, [Ru(η(6)-pcym)(bphen)(dca)]PF(6) (complex 1) and salinomycin, one of the most selective CSC-targeting compounds hitherto identified. Furthermore, Os(II) complex 2 reduces the formation, size, and viability of three-dimensional mammospheres which more closely reflect the tumor microenvironment than cells in traditional two-dimensional cultures. The antiproliferation studies and propidium iodide staining using flow cytometry suggest that Os(II) complex 2 induces human breast cancer stem cell death predominantly by necroptosis, a programmed form of necrosis. The results of this study demonstrate the promise of Os(II) complex 2 in treating human breast tumors. They also represent the foundation for further preclinical and clinical studies and applications of Os(II) complex 2 to comply with the emergent need for human breast CSCs-specific chemotherapeutics capable to treat chemotherapy-resistant and relapsed human breast tumors. Nature Publishing Group UK 2019-09-16 /pmc/articles/PMC6746710/ /pubmed/31527683 http://dx.doi.org/10.1038/s41598-019-49774-x Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Novohradsky, Vojtech
Markova, Lenka
Kostrhunova, Hana
Trávníček, Zdeněk
Brabec, Viktor
Kasparkova, Jana
An anticancer Os(II) bathophenanthroline complex as a human breast cancer stem cell-selective, mammosphere potent agent that kills cells by necroptosis
title An anticancer Os(II) bathophenanthroline complex as a human breast cancer stem cell-selective, mammosphere potent agent that kills cells by necroptosis
title_full An anticancer Os(II) bathophenanthroline complex as a human breast cancer stem cell-selective, mammosphere potent agent that kills cells by necroptosis
title_fullStr An anticancer Os(II) bathophenanthroline complex as a human breast cancer stem cell-selective, mammosphere potent agent that kills cells by necroptosis
title_full_unstemmed An anticancer Os(II) bathophenanthroline complex as a human breast cancer stem cell-selective, mammosphere potent agent that kills cells by necroptosis
title_short An anticancer Os(II) bathophenanthroline complex as a human breast cancer stem cell-selective, mammosphere potent agent that kills cells by necroptosis
title_sort anticancer os(ii) bathophenanthroline complex as a human breast cancer stem cell-selective, mammosphere potent agent that kills cells by necroptosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6746710/
https://www.ncbi.nlm.nih.gov/pubmed/31527683
http://dx.doi.org/10.1038/s41598-019-49774-x
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