Cargando…
Cannabimimetic N-Stearoylethanolamine as “Double-Edged Sword” in Anticancer Chemotherapy: Proapoptotic Effect on Tumor Cells and Suppression of Tumor Growth versus Its Bio-Protective Actions in Complex with Polymeric Carrier on General Toxicity of Doxorubicin In Vivo
This study reports a dose-dependent pro-apoptotic action of synthetic cannabimimetic N-stearoylethanolamine (NSE) on diverse cancer cell lines, including multidrug-resistant models. No antioxidant or cytoprotective effects of NSE were found when it was applied together with doxorubicin. A complex of...
Autores principales: | , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10055797/ https://www.ncbi.nlm.nih.gov/pubmed/36986696 http://dx.doi.org/10.3390/pharmaceutics15030835 |
_version_ | 1785015961272713216 |
---|---|
author | Panchuk, Rostyslav Skorokhyd, Nadiya Chumak, Vira Lehka, Lilya Kosiakova, Halyna Horid’ko, Tetyana Hudz, Iehor Hula, Nadiya Riabtseva, Anna Mitina, Nataliya Zaichenko, Alexander Heffeter, Petra Berger, Walter Stoika, Rostyslav |
author_facet | Panchuk, Rostyslav Skorokhyd, Nadiya Chumak, Vira Lehka, Lilya Kosiakova, Halyna Horid’ko, Tetyana Hudz, Iehor Hula, Nadiya Riabtseva, Anna Mitina, Nataliya Zaichenko, Alexander Heffeter, Petra Berger, Walter Stoika, Rostyslav |
author_sort | Panchuk, Rostyslav |
collection | PubMed |
description | This study reports a dose-dependent pro-apoptotic action of synthetic cannabimimetic N-stearoylethanolamine (NSE) on diverse cancer cell lines, including multidrug-resistant models. No antioxidant or cytoprotective effects of NSE were found when it was applied together with doxorubicin. A complex of NSE with the polymeric carrier poly(5-(tert-butylperoxy)-5-methyl-1-hexen-3-yn-co-glycidyl methacrylate)-graft-PEG was synthesized. Co-immobilization of NSE and doxorubicin on this carrier led to a 2-10-fold enhancement of the anticancer activity, particularly, against drug-resistant cells overexpressing ABCC1 and ABCB1. This effect might be caused by accelerated nuclear accumulation of doxorubicin in cancer cells, which led to the activation of the caspase cascade, revealed by Western blot analysis. The NSE-containing polymeric carrier was also able to significantly enhance the therapeutic activity of doxorubicin in mice with implanted NK/Ly lymphoma or L1210 leukemia, leading to the complete eradication of these malignancies. Simultaneously, loading to the carrier prevented doxorubicin-induced elevation of AST and ALT as well as leukopenia in healthy Balb/c mice. Thus, a unique bi-functionality of the novel pharmaceutical formulation of NSE was revealed. It enhanced doxorubicin-induced apoptosis in cancer cells in vitro and promoted its anticancer activity against lymphoma and leukemia models in vivo. Simultaneously, it was very well tolerated preventing frequently observed doxorubicin-associated adverse effects. |
format | Online Article Text |
id | pubmed-10055797 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-100557972023-03-30 Cannabimimetic N-Stearoylethanolamine as “Double-Edged Sword” in Anticancer Chemotherapy: Proapoptotic Effect on Tumor Cells and Suppression of Tumor Growth versus Its Bio-Protective Actions in Complex with Polymeric Carrier on General Toxicity of Doxorubicin In Vivo Panchuk, Rostyslav Skorokhyd, Nadiya Chumak, Vira Lehka, Lilya Kosiakova, Halyna Horid’ko, Tetyana Hudz, Iehor Hula, Nadiya Riabtseva, Anna Mitina, Nataliya Zaichenko, Alexander Heffeter, Petra Berger, Walter Stoika, Rostyslav Pharmaceutics Article This study reports a dose-dependent pro-apoptotic action of synthetic cannabimimetic N-stearoylethanolamine (NSE) on diverse cancer cell lines, including multidrug-resistant models. No antioxidant or cytoprotective effects of NSE were found when it was applied together with doxorubicin. A complex of NSE with the polymeric carrier poly(5-(tert-butylperoxy)-5-methyl-1-hexen-3-yn-co-glycidyl methacrylate)-graft-PEG was synthesized. Co-immobilization of NSE and doxorubicin on this carrier led to a 2-10-fold enhancement of the anticancer activity, particularly, against drug-resistant cells overexpressing ABCC1 and ABCB1. This effect might be caused by accelerated nuclear accumulation of doxorubicin in cancer cells, which led to the activation of the caspase cascade, revealed by Western blot analysis. The NSE-containing polymeric carrier was also able to significantly enhance the therapeutic activity of doxorubicin in mice with implanted NK/Ly lymphoma or L1210 leukemia, leading to the complete eradication of these malignancies. Simultaneously, loading to the carrier prevented doxorubicin-induced elevation of AST and ALT as well as leukopenia in healthy Balb/c mice. Thus, a unique bi-functionality of the novel pharmaceutical formulation of NSE was revealed. It enhanced doxorubicin-induced apoptosis in cancer cells in vitro and promoted its anticancer activity against lymphoma and leukemia models in vivo. Simultaneously, it was very well tolerated preventing frequently observed doxorubicin-associated adverse effects. MDPI 2023-03-03 /pmc/articles/PMC10055797/ /pubmed/36986696 http://dx.doi.org/10.3390/pharmaceutics15030835 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Panchuk, Rostyslav Skorokhyd, Nadiya Chumak, Vira Lehka, Lilya Kosiakova, Halyna Horid’ko, Tetyana Hudz, Iehor Hula, Nadiya Riabtseva, Anna Mitina, Nataliya Zaichenko, Alexander Heffeter, Petra Berger, Walter Stoika, Rostyslav Cannabimimetic N-Stearoylethanolamine as “Double-Edged Sword” in Anticancer Chemotherapy: Proapoptotic Effect on Tumor Cells and Suppression of Tumor Growth versus Its Bio-Protective Actions in Complex with Polymeric Carrier on General Toxicity of Doxorubicin In Vivo |
title | Cannabimimetic N-Stearoylethanolamine as “Double-Edged Sword” in Anticancer Chemotherapy: Proapoptotic Effect on Tumor Cells and Suppression of Tumor Growth versus Its Bio-Protective Actions in Complex with Polymeric Carrier on General Toxicity of Doxorubicin In Vivo |
title_full | Cannabimimetic N-Stearoylethanolamine as “Double-Edged Sword” in Anticancer Chemotherapy: Proapoptotic Effect on Tumor Cells and Suppression of Tumor Growth versus Its Bio-Protective Actions in Complex with Polymeric Carrier on General Toxicity of Doxorubicin In Vivo |
title_fullStr | Cannabimimetic N-Stearoylethanolamine as “Double-Edged Sword” in Anticancer Chemotherapy: Proapoptotic Effect on Tumor Cells and Suppression of Tumor Growth versus Its Bio-Protective Actions in Complex with Polymeric Carrier on General Toxicity of Doxorubicin In Vivo |
title_full_unstemmed | Cannabimimetic N-Stearoylethanolamine as “Double-Edged Sword” in Anticancer Chemotherapy: Proapoptotic Effect on Tumor Cells and Suppression of Tumor Growth versus Its Bio-Protective Actions in Complex with Polymeric Carrier on General Toxicity of Doxorubicin In Vivo |
title_short | Cannabimimetic N-Stearoylethanolamine as “Double-Edged Sword” in Anticancer Chemotherapy: Proapoptotic Effect on Tumor Cells and Suppression of Tumor Growth versus Its Bio-Protective Actions in Complex with Polymeric Carrier on General Toxicity of Doxorubicin In Vivo |
title_sort | cannabimimetic n-stearoylethanolamine as “double-edged sword” in anticancer chemotherapy: proapoptotic effect on tumor cells and suppression of tumor growth versus its bio-protective actions in complex with polymeric carrier on general toxicity of doxorubicin in vivo |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10055797/ https://www.ncbi.nlm.nih.gov/pubmed/36986696 http://dx.doi.org/10.3390/pharmaceutics15030835 |
work_keys_str_mv | AT panchukrostyslav cannabimimeticnstearoylethanolamineasdoubleedgedswordinanticancerchemotherapyproapoptoticeffectontumorcellsandsuppressionoftumorgrowthversusitsbioprotectiveactionsincomplexwithpolymericcarrierongeneraltoxicityofdoxorubicininvivo AT skorokhydnadiya cannabimimeticnstearoylethanolamineasdoubleedgedswordinanticancerchemotherapyproapoptoticeffectontumorcellsandsuppressionoftumorgrowthversusitsbioprotectiveactionsincomplexwithpolymericcarrierongeneraltoxicityofdoxorubicininvivo AT chumakvira cannabimimeticnstearoylethanolamineasdoubleedgedswordinanticancerchemotherapyproapoptoticeffectontumorcellsandsuppressionoftumorgrowthversusitsbioprotectiveactionsincomplexwithpolymericcarrierongeneraltoxicityofdoxorubicininvivo AT lehkalilya cannabimimeticnstearoylethanolamineasdoubleedgedswordinanticancerchemotherapyproapoptoticeffectontumorcellsandsuppressionoftumorgrowthversusitsbioprotectiveactionsincomplexwithpolymericcarrierongeneraltoxicityofdoxorubicininvivo AT kosiakovahalyna cannabimimeticnstearoylethanolamineasdoubleedgedswordinanticancerchemotherapyproapoptoticeffectontumorcellsandsuppressionoftumorgrowthversusitsbioprotectiveactionsincomplexwithpolymericcarrierongeneraltoxicityofdoxorubicininvivo AT horidkotetyana cannabimimeticnstearoylethanolamineasdoubleedgedswordinanticancerchemotherapyproapoptoticeffectontumorcellsandsuppressionoftumorgrowthversusitsbioprotectiveactionsincomplexwithpolymericcarrierongeneraltoxicityofdoxorubicininvivo AT hudziehor cannabimimeticnstearoylethanolamineasdoubleedgedswordinanticancerchemotherapyproapoptoticeffectontumorcellsandsuppressionoftumorgrowthversusitsbioprotectiveactionsincomplexwithpolymericcarrierongeneraltoxicityofdoxorubicininvivo AT hulanadiya cannabimimeticnstearoylethanolamineasdoubleedgedswordinanticancerchemotherapyproapoptoticeffectontumorcellsandsuppressionoftumorgrowthversusitsbioprotectiveactionsincomplexwithpolymericcarrierongeneraltoxicityofdoxorubicininvivo AT riabtsevaanna cannabimimeticnstearoylethanolamineasdoubleedgedswordinanticancerchemotherapyproapoptoticeffectontumorcellsandsuppressionoftumorgrowthversusitsbioprotectiveactionsincomplexwithpolymericcarrierongeneraltoxicityofdoxorubicininvivo AT mitinanataliya cannabimimeticnstearoylethanolamineasdoubleedgedswordinanticancerchemotherapyproapoptoticeffectontumorcellsandsuppressionoftumorgrowthversusitsbioprotectiveactionsincomplexwithpolymericcarrierongeneraltoxicityofdoxorubicininvivo AT zaichenkoalexander cannabimimeticnstearoylethanolamineasdoubleedgedswordinanticancerchemotherapyproapoptoticeffectontumorcellsandsuppressionoftumorgrowthversusitsbioprotectiveactionsincomplexwithpolymericcarrierongeneraltoxicityofdoxorubicininvivo AT heffeterpetra cannabimimeticnstearoylethanolamineasdoubleedgedswordinanticancerchemotherapyproapoptoticeffectontumorcellsandsuppressionoftumorgrowthversusitsbioprotectiveactionsincomplexwithpolymericcarrierongeneraltoxicityofdoxorubicininvivo AT bergerwalter cannabimimeticnstearoylethanolamineasdoubleedgedswordinanticancerchemotherapyproapoptoticeffectontumorcellsandsuppressionoftumorgrowthversusitsbioprotectiveactionsincomplexwithpolymericcarrierongeneraltoxicityofdoxorubicininvivo AT stoikarostyslav cannabimimeticnstearoylethanolamineasdoubleedgedswordinanticancerchemotherapyproapoptoticeffectontumorcellsandsuppressionoftumorgrowthversusitsbioprotectiveactionsincomplexwithpolymericcarrierongeneraltoxicityofdoxorubicininvivo |