Alternating Electric Fields (TTFields) Activate Cav1.2 Channels in Human Glioblastoma Cells

Abstract

Overview

Tumor Treating Fields (TTFields) is a contemporary FDA-approved therapy for both new and recurrent glioblastoma multiforme. This non-invasive treatment uses alternating electric fields of intermediate frequency and low intensity targeted at the tumor through electrode arrays.

Findings

• Investigation into TTFields' effects on Ca2+ signaling, ion channel function, cell cycle regulation, and clonogenic survival using various in vitro methods on human glioblastoma cell lines.
• Real-time RT-PCR was employed to assess the expression of voltage-gated Ca2+ channels, and both knock-down techniques and pharmacological interventions were used to determine their role in response to TTFields.
• Specific stimulation of Cav1.2-mediated Ca2+ entry by TTFields induced a range of responses including cell cycle arrest, mitochondrial membrane breakdown, DNA degradation, and a decrease in clonogenic survival, pointing to a potent tumoricidal effect.
• The inhibition of Cav1.2 augmented TTFields effects in one cell line, suggesting a significant role of Cav1.2 in cellular response to TTFields stress.

Conclusion

This study establishes Cav1.2 channels as a target of TTFields in the plasma membrane. The findings support a potential combination of TTFields treatment with clinical Ca2+ antagonists to enhance therapeutic outcomes.