AnvirzelTMregulates cell death through inhibiting GSK-3 activity in human U87 glioma cells
Sule Terzioglu-Usak1, Arife Nalli2, Birsen Elibol1
1Department of Medical Biology, Bezmialem Vakif University Medical School, Istanbul, Turkey.
Abstract:
Objectives: Cardiac glycosides are used as potential anti-cancer agents due to their effects on the inhibition of proliferation and induction of apoptosis and/or autophagy in cancer cells. Herein, we aimed to study the potential signaling pathways taken role in differential cell-death properties of AnvirzelTM which is consisted of two toxic cardiac glycosides (oleandrin and oleandrigenin), in U87 human glioblastoma cells.Methods: The anti-proliferative and anti-migratory effects of AnvirzelTM were assessed in U87 cells by WST-1 assay and wound healing assay, respectively. After treatment of AnvirzelTMwith doses of 10, 25, 50, 100 and 250 μg/ml, expression levels of proteins related to cell death were investigated by Western blot.Results: Anvirzel™ markedly inhibited the growth of U87 cells in a time- and dose-dependent manner following 24 h and 48 h treatments (p < 0.05). In addition, it was found that Anvirzel™ inhibited GSK-3, NOS and HIF1-α expressions whereas activated ERK in U87 cells compared to vehicle (p < 0.05).Discussion: The results suggested that AnvirzelTM regulated cell death distinctly from apoptosis in human glioblastoma cells. Further studies are required for validation of mechanistic insights about the potential signaling pathways taken role in differential cell death properties of AnvirzelTM.
Insights
Anvirzel™, a cardiac glycoside mixture, effectively inhibited U87 glioblastoma cell growth. It modulated cell death pathways by inhibiting GSK-3, NOS, and HIF1-α while activating ERK.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Cardiac glycosides show anti-cancer potential by inhibiting cancer cell proliferation and inducing apoptosis or autophagy.
- Anvirzel™ contains oleandrin and oleandrigenin, two toxic cardiac glycosides with potential anti-cancer applications.
Purpose of the Study:
- To investigate the signaling pathways involved in the differential cell death induced by Anvirzel™ in U87 human glioblastoma cells.
- To assess the anti-proliferative and anti-migratory effects of Anvirzel™ on U87 cells.
Main Methods:
- U87 cells were treated with varying doses of Anvirzel™ (10-250 μg/ml).
- Cell proliferation was measured using the WST-1 assay.
- Cell migration was assessed via wound healing assay.
- Protein expression related to cell death was analyzed using Western blot.
Main Results:
- Anvirzel™ significantly inhibited U87 cell growth in a time- and dose-dependent manner (24h and 48h treatments).
- Anvirzel™ treatment led to the inhibition of GSK-3, NOS, and HIF1-α protein expressions.
- Anvirzel™ treatment resulted in the activation of ERK signaling pathway in U87 cells.
Conclusions:
- Anvirzel™ exhibits anti-proliferative and anti-migratory effects on U87 glioblastoma cells.
- The compound appears to regulate cell death through mechanisms distinct from classical apoptosis.
- Further research is needed to fully elucidate the mechanistic insights into Anvirzel™'s cell death signaling pathways.
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