Cargando…
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...
Autores principales: | , , , , , , , , , , |
---|---|
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 |
_version_ | 1784857074555944960 |
---|---|
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. |
format | Online Article Text |
id | pubmed-9781439 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT trochopoulosantoniosgx micellarcurcuminsubstantiallyincreasestheantineoplasticactivityofthealkylphosphocholineerufosineagainsttwist1positivecutaneoustcelllymphomacelllines AT ilievayana micellarcurcuminsubstantiallyincreasestheantineoplasticactivityofthealkylphosphocholineerufosineagainsttwist1positivecutaneoustcelllymphomacelllines AT kroumovalexanderd micellarcurcuminsubstantiallyincreasestheantineoplasticactivityofthealkylphosphocholineerufosineagainsttwist1positivecutaneoustcelllymphomacelllines AT dimitrovalyudmilal micellarcurcuminsubstantiallyincreasestheantineoplasticactivityofthealkylphosphocholineerufosineagainsttwist1positivecutaneoustcelllymphomacelllines AT penchevaeltibiivanka micellarcurcuminsubstantiallyincreasestheantineoplasticactivityofthealkylphosphocholineerufosineagainsttwist1positivecutaneoustcelllymphomacelllines AT philipovstanislav micellarcurcuminsubstantiallyincreasestheantineoplasticactivityofthealkylphosphocholineerufosineagainsttwist1positivecutaneoustcelllymphomacelllines AT bergermartinr micellarcurcuminsubstantiallyincreasestheantineoplasticactivityofthealkylphosphocholineerufosineagainsttwist1positivecutaneoustcelllymphomacelllines AT najdenskihristom micellarcurcuminsubstantiallyincreasestheantineoplasticactivityofthealkylphosphocholineerufosineagainsttwist1positivecutaneoustcelllymphomacelllines AT yonchevakrassimira micellarcurcuminsubstantiallyincreasestheantineoplasticactivityofthealkylphosphocholineerufosineagainsttwist1positivecutaneoustcelllymphomacelllines AT konstantinovspirom micellarcurcuminsubstantiallyincreasestheantineoplasticactivityofthealkylphosphocholineerufosineagainsttwist1positivecutaneoustcelllymphomacelllines AT zaharievamayam micellarcurcuminsubstantiallyincreasestheantineoplasticactivityofthealkylphosphocholineerufosineagainsttwist1positivecutaneoustcelllymphomacelllines |