Optimizing Jasplakinolide delivery in rhabdomyosarcoma cells using pulsed electric fields (PEFs) for enhanced
Anna Szewczyk1, Nina Rembiałkowska2, Marta Migocka-Patrzałek3
1Department of Molecular and Cellular Biology, Faculty of Pharmacy, Wroclaw Medical University, Poland; State Research Institute Centre for Innovative Medicine, Department of Immunology and Bioelectrochemistry, Vilnius, Lithuania.
Abstract:
This study explores the combination of jasplakinolide with electroporation (JSP + EP), a method enhancing targeted molecule delivery. CHO-K1 (Chinese hamster ovarian), C2C12 (mouse myoblast), and RD (rhabdomyosarcoma) cells were treated with jasplakinolide (50 nM) in HEPES buffer and exposed to electrical pulses (0.8-1.2 kV/cm). Cell viability was measured via the MTS assay, cytoskeleton structure was assessed with confocal microscopy, and docking studies examined jasplakinolide-actin interactions. The combination of jasplakinolide and electric pulses synergistically affected RMS cells (Rhabdomyosarcoma), causing significant cytoskeletal changes and reduced viability. Docking studies revealed that jasplakinolide interacts with both monomeric and filamentous actin, highlighting a dual mechanism. Confocal imaging showed substantial actin cytoskeleton disruption in cancer cells, with minimal effects on normal cells. Jasplakinolide combined with electric pulses can specifically target cancer cells with less cytotoxicity to normal cells, potentially reducing side effects following the clinical procedure.
Insights
Jasplakinolide combined with electroporation shows promise for cancer therapy. This method targets cancer cells by disrupting their cytoskeleton, with minimal impact on normal cells, potentially reducing side effects.
Area of Science:
- Biochemistry
- Cell Biology
- Biotechnology
Background:
- Targeted molecule delivery is crucial for effective therapies.
- Jasplakinolide is known to affect actin dynamics.
- Electroporation enhances cellular uptake of molecules.
Purpose of the Study:
- To investigate the synergistic effects of jasplakinolide and electroporation (JSP + EP) on cancer cells.
- To assess the specificity of JSP + EP for cancer cells versus normal cells.
- To elucidate the mechanism of action of JSP + EP on the actin cytoskeleton.
Main Methods:
- Treatment of CHO-K1, C2C12, and RD cells with 50 nM jasplakinolide and electrical pulses (0.8-1.2 kV/cm).
- Cell viability assessed using the MTS assay.
- Cytoskeleton structure analyzed via confocal microscopy.
- Jasplakinolide-actin interactions studied using molecular docking.
Main Results:
- JSP + EP synergistically reduced viability and altered cytoskeletal structure in Rhabdomyosarcoma (RMS) cells.
- Docking studies confirmed jasplakinolide interacts with both monomeric and filamentous actin.
- Confocal imaging revealed significant actin cytoskeleton disruption in cancer cells, with minimal effects on normal cells.
Conclusions:
- Jasplakinolide combined with electroporation specifically targets cancer cells.
- This approach causes substantial actin cytoskeleton disruption in cancer cells.
- JSP + EP offers a potential strategy for cancer treatment with reduced cytotoxicity to normal cells.
