In Vitro Anti-Prostate Cancer Activity of Two Ebselen Analogues

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.

Influence of Ce3+ Substitution on Antimicrobial and Antibiofilm Properties of ZnCexFe2−xO4 Nanoparticles (X = 0.0, 0.02, 0.04, 0.06, and 0.08) Conjugated with Ebselen and Its Role Subsidised with γ-Radiation in Mitigating Human TNBC and Colorectal Adenocarcinoma Proliferation In Vitro

“…In the current study, we supplemented radiotherapy with theranostic nanoparticles constructed using several approaches such as by conjugating therapeutic agents to imaging nanoparticles, then imaging agents to therapeutic nanoparticles, and hence engineering unique nanoparticles possessing both therapeutic and diagnostic abilities [ 19 ]. Ebselen (Eb) ( N -phenyl-1,2-benzisoselenazol-3(2H)-one) is one of the organo-selenium compounds that mimics glutathione peroxidase and exhibits a wide range of biological activities including antibacterial, cyto-protective, anti-inflammatory, antioxidant, and anticancer activities [ 20 ]. In biomedical applications, nanoparticles have attracted attention due to their physiochemical properties such as appropriate size, large surface-to-mass ratios, high reactivity, and the ability to modify the biological influence of diffusivity and immunogenicity [ 21 ].…”

Ebselen and Analogues: Pharmacological Properties and Synthetic Strategies for Their Preparation

“…While compound 41 showed a fairly selective anti-proliferative activity, the methylbutyl-containing compound 42 was also able to exert cytotoxicity when tested in a non-cancerous PNT1A cell line [ 121 , 122 ]. The dynamic of the anti-prostate cancer inhibition of compound 42 was later studied in detail in a successive report by the same author [ 123 ].…”

Ebselen, a multi-target compound: its effects on biological processes and diseases

“…Recently, there have been numerous reports of ebselen derivatives, such as the organoselenium compound ( N -allyl-1,2-benzisoselenazol-3(2H)-one (N-allyl-BS)) and novel selenocyanates, having anti-tumour activity (Refs 148, 149). Seeking novel ebselen derivatives for the treatment of disease and to determine the molecular mechanism of their action is a promising line of research.…”