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Can oxysterols work in anti-glioblastoma therapy? Model studies complemented with biological experiments
Anita Wnętrzak1, Agata Kubisiak2, Anna Filiczkowska2
1Faculty of Chemistry, Jagiellonian University, Gronostajowa 2, 30-387 Kraków, Poland.
Abstract:
Despite the progress made in recent years in the field of oncology, the results of glioblastoma treatment remain unsatisfactory. In this paper, cholesterol derivatives - oxysterols - have been investigated in the context of their anti-cancer activity. First, the influence of three oxysterols (7-K, 7β-OH and 25-OH), differing in their chemical structure, on the properties of a model membrane imitating glioblastoma multiforme (GBM) cells was investigated. For this purpose, the Langmuir monolayer technique was applied. The obtained results clearly show that oxysterols modify the structure of the membrane by its stiffening, with the 7-K effect being the most pronounced. Next, the influence of 7-K on the nanomechanical properties of glioblastoma cells (U-251 line) was verified with AFM. It has been shown that 7-K has a dose-dependent cytotoxic effect on glioblastoma cells leading to the induction of apoptosis as confirmed by viability tests. Interestingly, significant changes in membrane structure, characteristic for phospholipidosis, has also been observed. Based on our results we believe that oxysterol-induced apoptosis and phospholipidosis are related and may share common signaling pathways. Dysregulation of lipids in phospholipidosis inhibit cell proliferation and may play key roles in the induction of apoptosis by oxysterols. Moreover, anticancer activity of these compounds may be related to the immobilization of cancer cells as a result of stiffening effect caused by oxysterols. Therefore, we believe that oxysterols are good candidates as new therapeutic molecules as an alternative to the aggressive treatment of GBM currently in use.
Insights
Oxysterols, cholesterol derivatives, show anti-cancer effects by stiffening glioblastoma cell membranes and inducing apoptosis. These findings suggest oxysterols as potential new therapies for glioblastoma multiforme (GBM).
Area of Science:
- Oncology
- Biochemistry
- Cell Biology
Background:
- Glioblastoma treatment outcomes remain poor despite advancements.
- Oxysterols, cholesterol derivatives, are explored for their anti-cancer potential.
Purpose of the Study:
- Investigate the anti-cancer activity of oxysterols against glioblastoma.
- Determine the effects of specific oxysterols on glioblastoma cell membranes and nanomechanical properties.
Main Methods:
- Langmuir monolayer technique to study model membranes.
- Atomic Force Microscopy (AFM) to assess nanomechanical properties.
- Cell viability assays to confirm apoptosis induction.
Main Results:
- Oxysterols stiffened model glioblastoma membranes, with 7-K having the most significant effect.
- 7-K demonstrated dose-dependent cytotoxicity, inducing apoptosis in U-251 glioblastoma cells.
- Observed phospholipidosis-like changes in cell membranes, suggesting a link with oxysterol-induced apoptosis.
Conclusions:
- Oxysterols exhibit anti-cancer properties against glioblastoma through apoptosis induction and membrane stiffening.
- Oxysterol-induced phospholipidosis may contribute to inhibiting cell proliferation and inducing apoptosis.
- Oxysterols are promising candidates for novel glioblastoma therapies, potentially offering an alternative to aggressive treatments.
