New Steroidal Selenides as Proapoptotic Factors

Izabella Jastrzebska; Natalia Wawrusiewicz-Kurylonek; Paweł A Grześ; Artur Ratkiewicz; Ewa Grabowska; Magdalena Czerniecka; Urszula Czyżewska; Adam Tylicki

doi:10.3390/molecules28227528

New Steroidal Selenides as Proapoptotic Factors

Molecules. 2023 Nov 10;28(22):7528. doi: 10.3390/molecules28227528.

Authors

Izabella Jastrzebska¹, Natalia Wawrusiewicz-Kurylonek², Paweł A Grześ¹, Artur Ratkiewicz¹, Ewa Grabowska³, Magdalena Czerniecka⁴, Urszula Czyżewska⁴, Adam Tylicki⁴

Affiliations

¹ Faculty of Chemistry, University of Białystok, Ciołkowskiego 1K, 15-245 Białystok, Poland.
² Department of Clinical Genetics, Medical University of Białystok, Waszyngtona 13, 15-089 Białystok, Poland.
³ Doctoral School of Exact and Natural Sciences, University of Bialystok, K. Ciolkowskiego 1K, 15-245 Bialystok, Poland.
⁴ Faculty of Biology, University of Białystok, Ciołkowskiego 1J, 15-245 Białystok, Poland.

Abstract

Cytostatic and pro-apoptotic effects of selenium steroid derivatives against HeLa cells were determined. The highest cytostatic activity was shown by derivative 4 (GI₅₀ 25.0 µM, almost complete growth inhibition after three days of culture, and over 97% of apoptotic and dead cells at 200 µM). The results of our study (cell number measurements, apoptosis profile, relative expression of apoptosis-related APAF1, BID, and mevalonate pathway-involved HMGCR, SQLE, CYP51A1, and PDHB genes, and computational chemistry data) support the hypothesis that tested selenosteroids induce the extrinsic pathway of apoptosis by affecting the cell membrane as cholesterol antimetabolites. An additional mechanism of action is possible through a direct action of derivative 4 to inhibit PDHB expression in a way similar to steroid hormones.

Keywords: HeLa cells; antimetabolites; cell growth inhibition; gene expression; in vitro culture.

MeSH terms

Apoptosis
Cholesterol / metabolism
Cytostatic Agents* / pharmacology
HeLa Cells
Humans

Substances

Cytostatic Agents
Cholesterol

Grants and funding

This study was supported by the Ministry of Education and Science, Poland, as a part of subsidies for maintaining the research potential granted to the Faculty of Biology (SWB-8) and Faculty of Chemistry of the University of Białystok. The equipment used for the cell culture at the Laboratory of Tissue Culture was funded by the Ministry of Science and Higher Education (grant no. 8636/E342/R/2014; Restructuration of Faculty of Biology and Chemistry). This work was financed from a scientific project by the subsidy of the Medical University of Bialystok (B.SUB.23.306).