In vitro anti-prostate cancer activity of two ebselen analogues

Katarzyna B. Kaczor-Keller , Anna Pawlik , Jacek Scianowski , Agata Pacuła , Magdalena Obieziurska , Fabio Marcheggiani , Ilenia Cirilli , Luca Tiano , Jędrzej Antosiewicz

Abstract

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.
Author Katarzyna B. Kaczor-Keller
Katarzyna B. Kaczor-Keller,,
-
, Anna Pawlik (FB/DMBG)
Anna Pawlik,,
- Katedra Biologii i Genetyki Medycznej
, Jacek Scianowski
Jacek Scianowski,,
-
, Agata Pacuła
Agata Pacuła,,
-
, Magdalena Obieziurska
Magdalena Obieziurska,,
-
, Fabio Marcheggiani
Fabio Marcheggiani,,
-
, Ilenia Cirilli
Ilenia Cirilli,,
-
, Luca Tiano
Luca Tiano,,
-
, Jędrzej Antosiewicz
Jędrzej Antosiewicz,,
-
Journal seriesPharmaceuticals, ISSN 1424-8247, (N/A 100 pkt)
Issue year2020
Vol13
No3
Pages1-16
Publication size in sheets0.75
Article number47
Keywords in EnglishOrganoselenium compound, apoptosis, ROS, DNA damage, chemoprevention
ASJC Classification1313 Molecular Medicine; 3003 Pharmaceutical Science
DOIDOI:10.3390/ph13030047
Languageen angielski
LicenseRepository; published final; Uznanie Autorstwa (CC-BY); with publication
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Kaczor_Keller_Katarzyna_In_vitro_antiprostate_2020.pdf Kaczor_Keller_Katarzyna_In_vitro_antiprostate_2020.pdf 5,4 MB
Score (nominal)100
Score sourcejournalList
ScoreMinisterial score = 100.0, 25-07-2020, ArticleFromJournal
Publication indicators WoS Citations = 0.000; Scopus SNIP (Source Normalised Impact per Paper): 2018 = 1.234
Citation count*
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LicencjaUtwór jest udostępniany na licencji Creative Commons Uznanie autorstwa 4.0 Międzynarodowe (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/
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* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or Perish system.
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