In Vitro Anti-Prostate Cancer Activity of Two Ebselen Analogues.

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

doi:10.3390/ph13030047

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.

Highlights

The search for novel and more effective drugs for prostate cancer treatment has been going on for decades, yet the progress in curing tumors is marginal
The purpose of the current study was to evaluate the mechanism of anticancer activity of N-allyl-benzisoselenazol-3(2H)-one(N-allyl-BS) and N-(3-methylbutyl)-1,2-benzisoselenazol-3(2H)-one (N-(3-mb)-BS) in prostate cancer cells, in order to fully assess its potential as an effective antitumor agent
We investigated the effect of the organoselenium compounds (OSCs) on the two prostate cancer cell lines, DU145 and PC-3, as well as PNT1A cells, to evaluate its effect on normal cells

Summary

Introduction

The search for novel and more effective drugs for prostate cancer treatment has been going on for decades, yet the progress in curing tumors is marginal. Prostate cancer has been listed as the second leading cause of male death in the US and western countries, but its incidence is high in other regions of the world, according to GLOBOCAN statistics [1]. These figures highlight the urge of novel and potent chemotherapeutics against prostate malignancies. Ebselen [N-phenyl-1,2-benzisoselenazol-3(2H)-one] is one of the most extensively studied organoselenium compounds (OSCs) It exhibits versatile biological activities, including anti-inflammatory, anti-bacterial, cytoprotective, neuroprotective, and anticancer activities. The anticancer activity might play an important role in cancer chemoprevention

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