Work

Optimizing Jasplakinolide delivery in rhabdomyosarcoma cells using pulsed electric fields (PEFs) for enhanced therapeutic impact

Year: 2025

Type: article

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. • The combination of jasplakinolide and electroporation (JSP + EP) selectively reduces rhabdomyosarcoma (RMS) cell viability, inducing significant cytoskeletal disruptions in cancer cells while sparing normal cells. • Electroporation, also the low-intensity electric pulses (0.8 kV/cm), significantly enhances the cytotoxic effects of jasplakinolide on rhabdomyosarcoma (RD) cells by promoting efficient entry and cytoskeletal disruption without excessive membrane damage. • Confocal microscopy and docking studies demonstrate that jasplakinolide targets both monomeric and filamentous actin, revealing a dual mechanism that disrupts the actin cytoskeleton, primarily in cancer cells. • This study reveals a dose-dependent relationship between pulse intensity and jasplakinolide efficacy, highlighting the importance of optimizing pulse parameters to maximize therapeutic impact on cancer cells while minimizing unintended cellular responses.

Source: Bioelectrochemistry

DOI: 10.1016/j.bioelechem.2025.108969