An apoptosis targeted stimulus with nanosecond pulsed electric fields (nsPEFs) in E4 squamous cell carcinoma

Area of Science:

• Biophysics
• Cell Biology
• Oncology

Background:

• Cancer cells often evade apoptosis, a key mechanism for cell death.
• Targeting apoptosis pathways is a promising strategy for cancer treatment.
• Understanding cell death induction mechanisms is crucial for developing novel therapies.

Purpose of the Study:

• To investigate the effects of nanosecond pulsed electric fields (nsPEFs) on apoptosis in E4 squamous carcinoma cells (SCC).
• To determine the electric field thresholds and kinetics of apoptosis-related events.
• To elucidate the specific pathways involved in nsPEF-induced cell death.

Main Methods:

• Exposure of E4 SCC to ten 300 ns pulses at varying electric fields.
• Quantification of cell death and apoptosis markers including phosphatidylserine externalization, caspase and calpain activation, cytochrome c release, Bid cleavage, and mitochondrial membrane potential.
• Assessment of the roles of intracellular and extracellular calcium in Bid cleavage.

Main Results:

• Over 95% cell death was achieved at high electric fields.
• Cell death was associated with phosphatidylserine externalization, caspase/calpain activation, and decreased Bid/mitochondrial membrane potential.
• Bid cleavage was predominantly dependent on caspase and extracellular calcium (extrinsic pathways).

Conclusions:

• nsPEFs are effective in inducing heterogeneous cancer cell death.
• Apoptosis is triggered through both intrinsic and extrinsic-like pathways, with extrinsic pathways playing a larger role.
• Caspase-associated cell death is a major, but not exclusive, mechanism in nsPEF-induced E4 SCC death.