Non-apoptotic cell death induction via sapogenin based supramolecular particles
Göklem Üner1, Erdal Bedir2, Onur Serçinoğlu3
1Department of Bioengineering, Faculty of Engineering, İzmir Institute of Technology, 35430, Urla, İzmir, Turkey.
Scientific Reports
|August 16, 2022
Summary
Novel anticancer agent AG-08 forms particles, triggering unique cell death. This discovery offers new therapeutic strategies for cancer treatment, overcoming resistance and heterogeneity.
Area of Science:
- Oncology
- Nanotechnology
- Molecular Biology
Background:
- Novel chemotherapeutics are crucial for overcoming tumor heterogeneity and therapeutic resistance.
- A previously reported saponin analog, AG-08, induces non-canonical necrotic cell death, showing promise for cancer therapy.
Purpose of the Study:
- To elucidate the mechanism of action for the novel chemotherapeutic AG-08.
- To identify the structural requirements for AG-08's unique cell death induction and particle formation.
Main Methods:
- Investigated AG-08's ability to form supramolecular particles.
- Analyzed particle internalization pathways using endocytosis.
- Utilized microarray analysis to identify affected cell signaling pathways.
- Synthesized and tested 18 analogs of AG-08.
Main Results:
- AG-08's unique cell death mechanism is triggered by its ability to form supramolecular particles.
- These particles are internalized via a distinct endocytosis pathway.
- AG-08 supramolecular structures impact cell signaling pathways, including unfolded protein response, immune response, and oxidative stress.
- Specific structural features were identified as essential for particle formation and cell death induction.
Conclusions:
- Supramolecular assemblies of small molecules represent a promising avenue for anticancer drug development.
- The findings challenge the conventional view of supramolecular assemblies as mere nuisances in drug discovery.
- AG-08's mechanism offers a novel approach to cancer therapy, distinct from existing treatments.
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