Cargando…

Anticancer Activity of Amantadine and Evaluation of Its Interactions with Selected Cytostatics in Relation to Human Melanoma Cells

Patients with Parkinson’s disease are prone to a higher incidence of melanoma. Amantadine (an anti-Parkinson drug) possesses the antiproliferative potential that can be favorable when combined with other chemotherapeutics. Cisplatin (CDDP) and mitoxantrone (MTO) are drugs used in melanoma chemothera...

Descripción completa

Detalles Bibliográficos
Autores principales: Krasowska, Danuta, Gerkowicz, Agnieszka, Wróblewska-Łuczka, Paula, Grabarska, Aneta, Załuska-Ogryzek, Katarzyna, Krasowska, Dorota, Łuszczki, Jarogniew J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9319452/
https://www.ncbi.nlm.nih.gov/pubmed/35886997
http://dx.doi.org/10.3390/ijms23147653
_version_ 1784755552759316480
author Krasowska, Danuta
Gerkowicz, Agnieszka
Wróblewska-Łuczka, Paula
Grabarska, Aneta
Załuska-Ogryzek, Katarzyna
Krasowska, Dorota
Łuszczki, Jarogniew J.
author_facet Krasowska, Danuta
Gerkowicz, Agnieszka
Wróblewska-Łuczka, Paula
Grabarska, Aneta
Załuska-Ogryzek, Katarzyna
Krasowska, Dorota
Łuszczki, Jarogniew J.
author_sort Krasowska, Danuta
collection PubMed
description Patients with Parkinson’s disease are prone to a higher incidence of melanoma. Amantadine (an anti-Parkinson drug) possesses the antiproliferative potential that can be favorable when combined with other chemotherapeutics. Cisplatin (CDDP) and mitoxantrone (MTO) are drugs used in melanoma chemotherapy, but they have many side effects. (1) Clinical observations revealed a high incidence of malignant melanoma in patients with Parkinson’s disease. Amantadine as an anti-Parkinson drug alleviates symptoms of Parkinson’s disease and theoretically, it should have anti-melanoma properties. (2) To characterize the interaction profile for combinations of amantadine with CDDP and MTO in four human melanoma cell lines (A375, SK-MEL 28, FM55P and FM55M2), type I isobolographic analysis was used in the MTT test. (3) Amantadine produces the anti-proliferative effects in various melanoma cell lines. Flow cytometry analysis indicated that amantadine induced apoptosis and G1/S phase cell cycle arrest. Western blotting analysis showed that amantadine markedly decreased cyclin-D1 protein levels and increased p21 levels. Additionally, amantadine significantly increased the Bax/Bcl-2 ratio. The combined application of amantadine with CDDP at the fixed-ratio of 1:1 exerted an additive interaction in the four studied cell lines in the MTT test. In contrast, the combination of amantadine with MTO (ratio of 1:1) produced synergistic interaction in the FM55M2 cell line in the MTT (* p < 0.05). The combination of amantadine with MTO was also additive in the remaining tested cell lines (A375, FM55P and SK-MEL28) in the MTT test. (4) Amantadine combined with MTO exerted the most desirable synergistic interaction, as assessed isobolographically. Additionally, the exposure of melanoma cell lines to amantadine in combination with CDDP or MTO augmented the induction of apoptosis mediated by amantadine alone.
format Online
Article
Text
id pubmed-9319452
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-93194522022-07-27 Anticancer Activity of Amantadine and Evaluation of Its Interactions with Selected Cytostatics in Relation to Human Melanoma Cells Krasowska, Danuta Gerkowicz, Agnieszka Wróblewska-Łuczka, Paula Grabarska, Aneta Załuska-Ogryzek, Katarzyna Krasowska, Dorota Łuszczki, Jarogniew J. Int J Mol Sci Article Patients with Parkinson’s disease are prone to a higher incidence of melanoma. Amantadine (an anti-Parkinson drug) possesses the antiproliferative potential that can be favorable when combined with other chemotherapeutics. Cisplatin (CDDP) and mitoxantrone (MTO) are drugs used in melanoma chemotherapy, but they have many side effects. (1) Clinical observations revealed a high incidence of malignant melanoma in patients with Parkinson’s disease. Amantadine as an anti-Parkinson drug alleviates symptoms of Parkinson’s disease and theoretically, it should have anti-melanoma properties. (2) To characterize the interaction profile for combinations of amantadine with CDDP and MTO in four human melanoma cell lines (A375, SK-MEL 28, FM55P and FM55M2), type I isobolographic analysis was used in the MTT test. (3) Amantadine produces the anti-proliferative effects in various melanoma cell lines. Flow cytometry analysis indicated that amantadine induced apoptosis and G1/S phase cell cycle arrest. Western blotting analysis showed that amantadine markedly decreased cyclin-D1 protein levels and increased p21 levels. Additionally, amantadine significantly increased the Bax/Bcl-2 ratio. The combined application of amantadine with CDDP at the fixed-ratio of 1:1 exerted an additive interaction in the four studied cell lines in the MTT test. In contrast, the combination of amantadine with MTO (ratio of 1:1) produced synergistic interaction in the FM55M2 cell line in the MTT (* p < 0.05). The combination of amantadine with MTO was also additive in the remaining tested cell lines (A375, FM55P and SK-MEL28) in the MTT test. (4) Amantadine combined with MTO exerted the most desirable synergistic interaction, as assessed isobolographically. Additionally, the exposure of melanoma cell lines to amantadine in combination with CDDP or MTO augmented the induction of apoptosis mediated by amantadine alone. MDPI 2022-07-11 /pmc/articles/PMC9319452/ /pubmed/35886997 http://dx.doi.org/10.3390/ijms23147653 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
Krasowska, Danuta
Gerkowicz, Agnieszka
Wróblewska-Łuczka, Paula
Grabarska, Aneta
Załuska-Ogryzek, Katarzyna
Krasowska, Dorota
Łuszczki, Jarogniew J.
Anticancer Activity of Amantadine and Evaluation of Its Interactions with Selected Cytostatics in Relation to Human Melanoma Cells
title Anticancer Activity of Amantadine and Evaluation of Its Interactions with Selected Cytostatics in Relation to Human Melanoma Cells
title_full Anticancer Activity of Amantadine and Evaluation of Its Interactions with Selected Cytostatics in Relation to Human Melanoma Cells
title_fullStr Anticancer Activity of Amantadine and Evaluation of Its Interactions with Selected Cytostatics in Relation to Human Melanoma Cells
title_full_unstemmed Anticancer Activity of Amantadine and Evaluation of Its Interactions with Selected Cytostatics in Relation to Human Melanoma Cells
title_short Anticancer Activity of Amantadine and Evaluation of Its Interactions with Selected Cytostatics in Relation to Human Melanoma Cells
title_sort anticancer activity of amantadine and evaluation of its interactions with selected cytostatics in relation to human melanoma cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9319452/
https://www.ncbi.nlm.nih.gov/pubmed/35886997
http://dx.doi.org/10.3390/ijms23147653
work_keys_str_mv AT krasowskadanuta anticanceractivityofamantadineandevaluationofitsinteractionswithselectedcytostaticsinrelationtohumanmelanomacells
AT gerkowiczagnieszka anticanceractivityofamantadineandevaluationofitsinteractionswithselectedcytostaticsinrelationtohumanmelanomacells
AT wroblewskałuczkapaula anticanceractivityofamantadineandevaluationofitsinteractionswithselectedcytostaticsinrelationtohumanmelanomacells
AT grabarskaaneta anticanceractivityofamantadineandevaluationofitsinteractionswithselectedcytostaticsinrelationtohumanmelanomacells
AT załuskaogryzekkatarzyna anticanceractivityofamantadineandevaluationofitsinteractionswithselectedcytostaticsinrelationtohumanmelanomacells
AT krasowskadorota anticanceractivityofamantadineandevaluationofitsinteractionswithselectedcytostaticsinrelationtohumanmelanomacells
AT łuszczkijarogniewj anticanceractivityofamantadineandevaluationofitsinteractionswithselectedcytostaticsinrelationtohumanmelanomacells