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Micellar Curcumin Substantially Increases the Antineoplastic Activity of the Alkylphosphocholine Erufosine against TWIST1 Positive Cutaneous T Cell Lymphoma Cell Lines

Cutaneous T-cell lymphoma (CTCL) is a rare form of cancer with local as well as systemic manifestations. Concomitant bacterial infections increase morbidity and mortality rates due to impaired skin barrier and immune deficiency. In the current study, we demonstrated that the in vitro anti-lymphoma p...

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Autores principales: Trochopoulos, Antonios G. X., Ilieva, Yana, Kroumov, Alexander D., Dimitrova, Lyudmila L., Pencheva-El Tibi, Ivanka, Philipov, Stanislav, Berger, Martin R., Najdenski, Hristo M., Yoncheva, Krassimira, Konstantinov, Spiro M., Zaharieva, Maya M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9781439/
https://www.ncbi.nlm.nih.gov/pubmed/36559182
http://dx.doi.org/10.3390/pharmaceutics14122688
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author Trochopoulos, Antonios G. X.
Ilieva, Yana
Kroumov, Alexander D.
Dimitrova, Lyudmila L.
Pencheva-El Tibi, Ivanka
Philipov, Stanislav
Berger, Martin R.
Najdenski, Hristo M.
Yoncheva, Krassimira
Konstantinov, Spiro M.
Zaharieva, Maya M.
author_facet Trochopoulos, Antonios G. X.
Ilieva, Yana
Kroumov, Alexander D.
Dimitrova, Lyudmila L.
Pencheva-El Tibi, Ivanka
Philipov, Stanislav
Berger, Martin R.
Najdenski, Hristo M.
Yoncheva, Krassimira
Konstantinov, Spiro M.
Zaharieva, Maya M.
author_sort Trochopoulos, Antonios G. X.
collection PubMed
description Cutaneous T-cell lymphoma (CTCL) is a rare form of cancer with local as well as systemic manifestations. Concomitant bacterial infections increase morbidity and mortality rates due to impaired skin barrier and immune deficiency. In the current study, we demonstrated that the in vitro anti-lymphoma potential of erufosine is diminished by TWIST1 expression and micellar curcumin substantially increases its antineoplastic activity. Pharmacokinetic analysis showed that the micellar curcumin (MCRM) used in our study was characterized by low zeta potential, slow release of curcumin, and fast cell membrane penetration. The combination ratio 1:4 [erufosine:MCRM] achieved strong synergism by inhibiting cell proliferation and clonogenicity. The combined antiproliferative effects were calculated using the symbolic mathematical software MAPLE 15. The synergistic combination strongly decreased the expression of TWIST1 and protein kinase B/Akt as proven by western blotting. Significant reductions in NF-κB activation, induction of apoptosis, and altered glutathione levels were demonstrated by corresponding assays. In addition, the synergistic combination enhanced the anti-staphylococcal activity and prevented biofilm formation, as shown by crystal violet staining. Taken together, the above results show that the development of nanotechnological treatment modalities for CTCL, based on rational drug combinations exhibiting parallel antineoplastic and antibacterial effects, may prove efficacious.
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spelling pubmed-97814392022-12-24 Micellar Curcumin Substantially Increases the Antineoplastic Activity of the Alkylphosphocholine Erufosine against TWIST1 Positive Cutaneous T Cell Lymphoma Cell Lines Trochopoulos, Antonios G. X. Ilieva, Yana Kroumov, Alexander D. Dimitrova, Lyudmila L. Pencheva-El Tibi, Ivanka Philipov, Stanislav Berger, Martin R. Najdenski, Hristo M. Yoncheva, Krassimira Konstantinov, Spiro M. Zaharieva, Maya M. Pharmaceutics Article Cutaneous T-cell lymphoma (CTCL) is a rare form of cancer with local as well as systemic manifestations. Concomitant bacterial infections increase morbidity and mortality rates due to impaired skin barrier and immune deficiency. In the current study, we demonstrated that the in vitro anti-lymphoma potential of erufosine is diminished by TWIST1 expression and micellar curcumin substantially increases its antineoplastic activity. Pharmacokinetic analysis showed that the micellar curcumin (MCRM) used in our study was characterized by low zeta potential, slow release of curcumin, and fast cell membrane penetration. The combination ratio 1:4 [erufosine:MCRM] achieved strong synergism by inhibiting cell proliferation and clonogenicity. The combined antiproliferative effects were calculated using the symbolic mathematical software MAPLE 15. The synergistic combination strongly decreased the expression of TWIST1 and protein kinase B/Akt as proven by western blotting. Significant reductions in NF-κB activation, induction of apoptosis, and altered glutathione levels were demonstrated by corresponding assays. In addition, the synergistic combination enhanced the anti-staphylococcal activity and prevented biofilm formation, as shown by crystal violet staining. Taken together, the above results show that the development of nanotechnological treatment modalities for CTCL, based on rational drug combinations exhibiting parallel antineoplastic and antibacterial effects, may prove efficacious. MDPI 2022-12-01 /pmc/articles/PMC9781439/ /pubmed/36559182 http://dx.doi.org/10.3390/pharmaceutics14122688 Text en © 2022 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
Trochopoulos, Antonios G. X.
Ilieva, Yana
Kroumov, Alexander D.
Dimitrova, Lyudmila L.
Pencheva-El Tibi, Ivanka
Philipov, Stanislav
Berger, Martin R.
Najdenski, Hristo M.
Yoncheva, Krassimira
Konstantinov, Spiro M.
Zaharieva, Maya M.
Micellar Curcumin Substantially Increases the Antineoplastic Activity of the Alkylphosphocholine Erufosine against TWIST1 Positive Cutaneous T Cell Lymphoma Cell Lines
title Micellar Curcumin Substantially Increases the Antineoplastic Activity of the Alkylphosphocholine Erufosine against TWIST1 Positive Cutaneous T Cell Lymphoma Cell Lines
title_full Micellar Curcumin Substantially Increases the Antineoplastic Activity of the Alkylphosphocholine Erufosine against TWIST1 Positive Cutaneous T Cell Lymphoma Cell Lines
title_fullStr Micellar Curcumin Substantially Increases the Antineoplastic Activity of the Alkylphosphocholine Erufosine against TWIST1 Positive Cutaneous T Cell Lymphoma Cell Lines
title_full_unstemmed Micellar Curcumin Substantially Increases the Antineoplastic Activity of the Alkylphosphocholine Erufosine against TWIST1 Positive Cutaneous T Cell Lymphoma Cell Lines
title_short Micellar Curcumin Substantially Increases the Antineoplastic Activity of the Alkylphosphocholine Erufosine against TWIST1 Positive Cutaneous T Cell Lymphoma Cell Lines
title_sort micellar curcumin substantially increases the antineoplastic activity of the alkylphosphocholine erufosine against twist1 positive cutaneous t cell lymphoma cell lines
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9781439/
https://www.ncbi.nlm.nih.gov/pubmed/36559182
http://dx.doi.org/10.3390/pharmaceutics14122688
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