Combinatorial Anticancer Effects of the Non-Invasive High Voltage Micro-Second Pulse Electric Field with Low-Dose Curcumin on A549 Cells

Novel, alternative, and combinatorial approaches to combat cancer with minimal side effects are imperative due to the significant adverse effects associated with conventional therapies. The natural molecule curcumin has been reported to exhibit substantial anticancer activity against cancers, which are a leading cause of mortality worldwide. However, its clinical application is constrained by poor bioavailability. High Voltage Microsecond Pulse Electric Field (HV-µsPEF) therapy has emerged as a promising alternative in cancer treatment and may serve as an effective adjuvant anti-cancer modality. In the present study, the combinatorial effects of HV-µsPEF and low-dose curcumin on the A549 lung cancer cell line were evaluated with the primary objective of minimizing the curcumin dose required for its anticancer efficacy. HV-µsPEF was generated using a previously reported pulse generator and combined with low doses of curcumin to assess their effects on the A549 cell line. Cellular morphology was analyzed through phase-contrast microscopy, while flow cytometry was employed to evaluate the mode of cell death, curcumin uptake, Reactive Oxygen Species (ROS) levels, and Mitochondrial Membrane Potential (MMP) loss. The results demonstrated a highly synergistic induction of cell death in A549 cells, as observed through phase-contrast microscopy and flow-cytometry analyses, attributed to the enhanced uptake of curcumin by cancer cells in the presence of HV-µsPEF. This combinatorial treatment resulted in increased ROS production and significant MMP loss in A549 cancer cells. The findings indicate that combining HV-µsPEF with low doses of curcumin holds promising anticancer potential, effectively reducing the reliance on high doses of curcumin, which are often impractical to achieve in therapeutic applications.