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In Vitro Anti-Prostate Cancer Activity of Two Ebselen Analogues

Scientific research has been underway for decades in order to develop an effective anticancer drug, and it has become crucial to find a novel and effective chemotherapeutics in the case of prostate cancer treatment. Ebselen derivatives have been shown to possess a variety of biological activities, i...

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Autores principales: Kaczor-Keller, Katarzyna B., Pawlik, Anna, Scianowski, Jacek, Pacuła, Agata, Obieziurska, Magdalena, Marcheggiani, Fabio, Cirilli, Ilenia, Tiano, Luca, Antosiewicz, Jedrzej
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7151718/
https://www.ncbi.nlm.nih.gov/pubmed/32192052
http://dx.doi.org/10.3390/ph13030047
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author Kaczor-Keller, Katarzyna B.
Pawlik, Anna
Scianowski, Jacek
Pacuła, Agata
Obieziurska, Magdalena
Marcheggiani, Fabio
Cirilli, Ilenia
Tiano, Luca
Antosiewicz, Jedrzej
author_facet Kaczor-Keller, Katarzyna B.
Pawlik, Anna
Scianowski, Jacek
Pacuła, Agata
Obieziurska, Magdalena
Marcheggiani, Fabio
Cirilli, Ilenia
Tiano, Luca
Antosiewicz, Jedrzej
author_sort Kaczor-Keller, Katarzyna B.
collection PubMed
description Scientific research has been underway for decades in order to develop an effective anticancer drug, and it has become crucial to find a novel and effective chemotherapeutics in the case of prostate cancer treatment. Ebselen derivatives have been shown to possess a variety of biological activities, including cytostatic and cytotoxic action against tumor cells. In this study, the cytotoxic effect and anticancer mechanism of action of two organoselenium compounds— (N-allyl-1,2-benzisoselenazol-3(2H)-one (N-allyl-BS) and N-(3-methylbutyl)-1,2-benzisoselenazol-3(2H)-one) (N-(3-mb)-BS)—were investigated on two phenotypically different prostate cancer cell lines DU 145 and PC-3. The influence of analyzed compounds on the viability parameter was also assessed on normal prostate cell line PNT1A. The results showed that both organoselenium compounds (OSCs) efficiently inhibited cancer cell proliferation, whereas normal PNT1A cells were less sensitive to the analazyed ebselen analouges. Both OSCs induced G2/M cell cycle arrest and prompted cell death through apoptosis. The detection of cleaved Poly (ADP-ribose) Polymerase (PARP) confirmed this. In addition, N-allyl-BS and N-(3-m)-b-BS increased the level of reactive oxygen species (ROS) formation, however only N-allyl-BS induced DNA damage. Based on our data, we assume that OSCs’ anticancer action can be associated with oxidative stress induction and inactivation of the Akt- dependent signalling pathway. In conclusion, our data demonstrate that ebselen derivatives showed strong cytotoxic efficiency towards prostate cancer cells and may be elucidated as a novel, potent anticancer agent.
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spelling pubmed-71517182020-04-20 In Vitro Anti-Prostate Cancer Activity of Two Ebselen Analogues Kaczor-Keller, Katarzyna B. Pawlik, Anna Scianowski, Jacek Pacuła, Agata Obieziurska, Magdalena Marcheggiani, Fabio Cirilli, Ilenia Tiano, Luca Antosiewicz, Jedrzej Pharmaceuticals (Basel) Article Scientific research has been underway for decades in order to develop an effective anticancer drug, and it has become crucial to find a novel and effective chemotherapeutics in the case of prostate cancer treatment. Ebselen derivatives have been shown to possess a variety of biological activities, including cytostatic and cytotoxic action against tumor cells. In this study, the cytotoxic effect and anticancer mechanism of action of two organoselenium compounds— (N-allyl-1,2-benzisoselenazol-3(2H)-one (N-allyl-BS) and N-(3-methylbutyl)-1,2-benzisoselenazol-3(2H)-one) (N-(3-mb)-BS)—were investigated on two phenotypically different prostate cancer cell lines DU 145 and PC-3. The influence of analyzed compounds on the viability parameter was also assessed on normal prostate cell line PNT1A. The results showed that both organoselenium compounds (OSCs) efficiently inhibited cancer cell proliferation, whereas normal PNT1A cells were less sensitive to the analazyed ebselen analouges. Both OSCs induced G2/M cell cycle arrest and prompted cell death through apoptosis. The detection of cleaved Poly (ADP-ribose) Polymerase (PARP) confirmed this. In addition, N-allyl-BS and N-(3-m)-b-BS increased the level of reactive oxygen species (ROS) formation, however only N-allyl-BS induced DNA damage. Based on our data, we assume that OSCs’ anticancer action can be associated with oxidative stress induction and inactivation of the Akt- dependent signalling pathway. In conclusion, our data demonstrate that ebselen derivatives showed strong cytotoxic efficiency towards prostate cancer cells and may be elucidated as a novel, potent anticancer agent. MDPI 2020-03-17 /pmc/articles/PMC7151718/ /pubmed/32192052 http://dx.doi.org/10.3390/ph13030047 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kaczor-Keller, Katarzyna B.
Pawlik, Anna
Scianowski, Jacek
Pacuła, Agata
Obieziurska, Magdalena
Marcheggiani, Fabio
Cirilli, Ilenia
Tiano, Luca
Antosiewicz, Jedrzej
In Vitro Anti-Prostate Cancer Activity of Two Ebselen Analogues
title In Vitro Anti-Prostate Cancer Activity of Two Ebselen Analogues
title_full In Vitro Anti-Prostate Cancer Activity of Two Ebselen Analogues
title_fullStr In Vitro Anti-Prostate Cancer Activity of Two Ebselen Analogues
title_full_unstemmed In Vitro Anti-Prostate Cancer Activity of Two Ebselen Analogues
title_short In Vitro Anti-Prostate Cancer Activity of Two Ebselen Analogues
title_sort in vitro anti-prostate cancer activity of two ebselen analogues
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7151718/
https://www.ncbi.nlm.nih.gov/pubmed/32192052
http://dx.doi.org/10.3390/ph13030047
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