New Steroidal Selenides as Proapoptotic Factors.
Izabella Jastrzebska1, Natalia Wawrusiewicz-Kurylonek2, Paweł A Grześ1
1Faculty of Chemistry, University of Białystok, Ciołkowskiego 1K, 15-245 Białystok, Poland.
Molecules (Basel, Switzerland)
|November 25, 2023
Summary
Selenium steroid derivatives show potent cytostatic and pro-apoptotic effects. Derivative 4 significantly inhibits HeLa cell growth and induces apoptosis, acting as cholesterol antimetabolites and potentially inhibiting PDHB expression.
Area of Science:
- Biochemistry
- Cell Biology
- Medicinal Chemistry
Background:
- Steroid derivatives are explored for therapeutic potential.
- Selenium incorporation into steroids may modulate biological activity.
- Apoptosis pathways are key targets for cancer therapy.
Purpose of the Study:
- To evaluate the cytostatic and pro-apoptotic effects of selenium steroid derivatives on HeLa cells.
- To elucidate the mechanism of action, including apoptosis pathway involvement.
- To identify the most potent derivative for further investigation.
Main Methods:
- Cell viability assays (GI50 determination) and cell counting.
- Apoptosis profiling using flow cytometry.
- Gene expression analysis (APAF1, BID, HMGCR, SQLE, CYP51A1, PDHB) via RT-qPCR.
- Computational chemistry for mechanistic insights.
Main Results:
- Derivative 4 exhibited the highest cytostatic activity (GI50 25.0 µM) and induced over 97% apoptosis/cell death at 200 µM.
- Apoptosis-related genes (APAF1, BID) and mevalonate pathway genes (HMGCR, SQLE, CYP51A1, PDHB) showed altered expression.
- Data support selenosteroids acting as cholesterol antimetabolites, inducing extrinsic apoptosis.
Conclusions:
- Selenium steroid derivatives, particularly derivative 4, demonstrate significant anti-cancer effects against HeLa cells.
- The mechanism involves inducing extrinsic apoptosis, likely by disrupting cell membrane cholesterol homeostasis.
- Derivative 4 may also inhibit PDHB expression, suggesting a dual mode of action.
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