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Simultaneous defeat of MCF7 and MDA-MB-231 resistances by a hypericin PDT–tamoxifen hybrid therapy

Currently the greatest challenge in oncology is the lack of homogeneity of the lesions where different cell components respond differently to treatment. There is growing consensus that monotherapies are insufficient to eradicate the disease and there is an unmet need for more potent combinatorial tr...

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Autores principales: Theodossiou, Theodossis A., Ali, Muhammad, Grigalavicius, Mantas, Grallert, Beata, Dillard, Pierre, Schink, Kay Oliver, Olsen, Cathrine E., Wälchli, Sébastien, Inderberg, Else Marit, Kubin, Andreas, Peng, Qian, Berg, Kristian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6458138/
https://www.ncbi.nlm.nih.gov/pubmed/30993194
http://dx.doi.org/10.1038/s41523-019-0108-8
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author Theodossiou, Theodossis A.
Ali, Muhammad
Grigalavicius, Mantas
Grallert, Beata
Dillard, Pierre
Schink, Kay Oliver
Olsen, Cathrine E.
Wälchli, Sébastien
Inderberg, Else Marit
Kubin, Andreas
Peng, Qian
Berg, Kristian
author_facet Theodossiou, Theodossis A.
Ali, Muhammad
Grigalavicius, Mantas
Grallert, Beata
Dillard, Pierre
Schink, Kay Oliver
Olsen, Cathrine E.
Wälchli, Sébastien
Inderberg, Else Marit
Kubin, Andreas
Peng, Qian
Berg, Kristian
author_sort Theodossiou, Theodossis A.
collection PubMed
description Currently the greatest challenge in oncology is the lack of homogeneity of the lesions where different cell components respond differently to treatment. There is growing consensus that monotherapies are insufficient to eradicate the disease and there is an unmet need for more potent combinatorial treatments. We have previously shown that hypericin photodynamic therapy (HYP-PDT) triggers electron transport chain (ETC) inhibition in cell mitochondria. We have also shown that tamoxifen (TAM) enhances cytotoxicity in cells with high respiration, when combined with ETC inhibitors. Herein we introduce a synergistic treatment based on TAM chemotherapy and HYP-PDT. We tested this novel combinatorial treatment (HYPERTAM) in two metabolically different breast cancer cell lines, the triple-negative MDA-MB-231 and the estrogen-receptor-positive MCF7, the former being quite sensitive to HYP-PDT while the latter very responsive to TAM treatment. In addition, we investigated the mode of death, effect of lipid peroxidation, and the effect on cell metabolism. The results were quite astounding. HYPERTAM exhibited over 90% cytotoxicity in both cell lines. This cytotoxicity was in the form of both necrosis and autophagy, while high levels of lipid peroxidation were observed in both cell lines. We, consequently, translated our research to an in vivo pilot study encompassing the MDA-MB-231 and MCF7 tumor models in NOD SCID-γ immunocompromised mice. Both treatment cohorts responded very positively to HYPERTRAM, which significantly prolonged mice survival. HYPERTAM is a potent, synergistic modality, which may lay the foundations for a novel, composite anticancer treatment, effective in diverse tumor types.
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spelling pubmed-64581382019-04-16 Simultaneous defeat of MCF7 and MDA-MB-231 resistances by a hypericin PDT–tamoxifen hybrid therapy Theodossiou, Theodossis A. Ali, Muhammad Grigalavicius, Mantas Grallert, Beata Dillard, Pierre Schink, Kay Oliver Olsen, Cathrine E. Wälchli, Sébastien Inderberg, Else Marit Kubin, Andreas Peng, Qian Berg, Kristian NPJ Breast Cancer Article Currently the greatest challenge in oncology is the lack of homogeneity of the lesions where different cell components respond differently to treatment. There is growing consensus that monotherapies are insufficient to eradicate the disease and there is an unmet need for more potent combinatorial treatments. We have previously shown that hypericin photodynamic therapy (HYP-PDT) triggers electron transport chain (ETC) inhibition in cell mitochondria. We have also shown that tamoxifen (TAM) enhances cytotoxicity in cells with high respiration, when combined with ETC inhibitors. Herein we introduce a synergistic treatment based on TAM chemotherapy and HYP-PDT. We tested this novel combinatorial treatment (HYPERTAM) in two metabolically different breast cancer cell lines, the triple-negative MDA-MB-231 and the estrogen-receptor-positive MCF7, the former being quite sensitive to HYP-PDT while the latter very responsive to TAM treatment. In addition, we investigated the mode of death, effect of lipid peroxidation, and the effect on cell metabolism. The results were quite astounding. HYPERTAM exhibited over 90% cytotoxicity in both cell lines. This cytotoxicity was in the form of both necrosis and autophagy, while high levels of lipid peroxidation were observed in both cell lines. We, consequently, translated our research to an in vivo pilot study encompassing the MDA-MB-231 and MCF7 tumor models in NOD SCID-γ immunocompromised mice. Both treatment cohorts responded very positively to HYPERTRAM, which significantly prolonged mice survival. HYPERTAM is a potent, synergistic modality, which may lay the foundations for a novel, composite anticancer treatment, effective in diverse tumor types. Nature Publishing Group UK 2019-04-10 /pmc/articles/PMC6458138/ /pubmed/30993194 http://dx.doi.org/10.1038/s41523-019-0108-8 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
Theodossiou, Theodossis A.
Ali, Muhammad
Grigalavicius, Mantas
Grallert, Beata
Dillard, Pierre
Schink, Kay Oliver
Olsen, Cathrine E.
Wälchli, Sébastien
Inderberg, Else Marit
Kubin, Andreas
Peng, Qian
Berg, Kristian
Simultaneous defeat of MCF7 and MDA-MB-231 resistances by a hypericin PDT–tamoxifen hybrid therapy
title Simultaneous defeat of MCF7 and MDA-MB-231 resistances by a hypericin PDT–tamoxifen hybrid therapy
title_full Simultaneous defeat of MCF7 and MDA-MB-231 resistances by a hypericin PDT–tamoxifen hybrid therapy
title_fullStr Simultaneous defeat of MCF7 and MDA-MB-231 resistances by a hypericin PDT–tamoxifen hybrid therapy
title_full_unstemmed Simultaneous defeat of MCF7 and MDA-MB-231 resistances by a hypericin PDT–tamoxifen hybrid therapy
title_short Simultaneous defeat of MCF7 and MDA-MB-231 resistances by a hypericin PDT–tamoxifen hybrid therapy
title_sort simultaneous defeat of mcf7 and mda-mb-231 resistances by a hypericin pdt–tamoxifen hybrid therapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6458138/
https://www.ncbi.nlm.nih.gov/pubmed/30993194
http://dx.doi.org/10.1038/s41523-019-0108-8
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