In Vitro Anti-Prostate Cancer Activity of Two Ebselen Analogues
Katarzyna B Kaczor-Keller1, Anna Pawlik2, Jacek Scianowski3
1Department of Bioenergetics and Physiology of Exercise, Medical University of Gdansk, 80-211 Gdansk, Poland.
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.
Insights
Two novel organoselenium compounds (OSCs) effectively inhibit prostate cancer cell growth by inducing apoptosis and cell cycle arrest. These ebselen derivatives show promise as potent anticancer agents with reduced toxicity to normal cells.
Area of Science:
- Medicinal Chemistry
- Oncology
- Cell Biology
Background:
- Prostate cancer treatment requires novel chemotherapeutics.
- Ebselen derivatives exhibit cytostatic and cytotoxic activities against tumor cells.
Purpose of the Study:
- Investigate the anticancer mechanisms of two organoselenium compounds (OSCs): 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).
- Evaluate their effects on prostate cancer cell lines (DU 145, PC-3) and normal prostate cells (PNT1A).
Main Methods:
- Assessed cell viability and proliferation.
- Analyzed cell cycle progression (G2/M arrest).
- Detected apoptosis markers (cleaved PARP) and reactive oxygen species (ROS) levels.
- Investigated DNA damage and Akt signaling pathway involvement.
Main Results:
- Both OSCs significantly inhibited proliferation in DU 145 and PC-3 cells, with lower sensitivity in PNT1A cells.
- OSCs induced G2/M cell cycle arrest and apoptosis, confirmed by cleaved PARP.
- N-allyl-BS and N-(3-mb)-BS increased ROS; N-allyl-BS also induced DNA damage.
- Anticancer effects are linked to oxidative stress and Akt pathway inactivation.
Conclusions:
- Ebselen derivatives demonstrate potent cytotoxic effects against prostate cancer cells.
- These compounds represent promising novel anticancer agents for prostate cancer therapy.
