Targeting Cholangiocarcinoma Cells By Cold Piezoelectric Plasmas: In Vitro Efficacy And Cellular Mechanisms

TL;DR

This study explores cold piezoelectric plasma (CPP) as a novel, portable cancer therapy targeting cholangiocarcinoma cells, demonstrating immediate cytoskeleton effects and long-term DNA damage leading to cell death in vitro.

Contribution

It introduces the application of CPP with corona and dielectric barrier discharges against cholangiocarcinoma, highlighting its efficacy and cellular mechanisms.

Findings

CPP causes temperature gradients in cell cultures.

Pz-CD heats more but cools quickly after plasma stops.

CPP induces DNA damage and cell death in cancer cells.

Abstract

Cold piezoelectric plasma (CPP) is a novel approach in cancer therapy, enabling the development of portable treatment devices capable of triggering cancer cell death. While its effectiveness remains underexplored, this research focuses on its application against cholangiocarcinoma (CCA), an aggressive cancer of the biliary tract. A CPP device is utilized to generate either a corona discharge (Pz-CD) or a dielectric barrier discharge (Pz-DBD) for in vitro experiments. Notably, Pz-CD can deliver more power than Pz-DBD, although both sources produce significant levels of reactive species in plasma and liquid phases. This work shows that CPP causes a gradient increase in medium temperature from the center towards the edges of the culture well, especially for longer treatment times. Although Pz-CD heats more significantly, it cools quickly after plasma extinction. When applied to human CCA cells, CPP shows immediate and long-term effects, more localized for Pz-CD, while more uniform for Pz-DBD. Immediate effects result also in actin cytoskeleton remodeling without alteration of the cell membrane permeability. Long-term effects of CPP, although the antioxidant system is engaged, include activation of the DNA damage response pathway leading to cell death. In conclusion, CPP should be recognized as a promising antitumor therapy.