Differential Effects of Cold Atmospheric Plasma in the Treatment of Malignant Glioma

Abstract

ObjectiveCold atmospheric plasma (CAP) has recently been shown to selectively target cancer cells with minimal effects on normal cells. We systematically assessed the effects of CAP in the treatment of glioblastoma.MethodsThree glioma cell lines, normal astrocytes, and endothelial cell lines were treated with CAP. The effects of CAP were then characterized for viability, cytotoxicity/apoptosis, and cell cycle effects. Statistical significance was determined with student's t-test.ResultsCAP treatment decreases viability of glioma cells in a dose dependent manner, with the ID50 between 90-120 seconds for all glioma cell lines. Treatment with CAP for more than 120 seconds resulted in viability less than 35% at 24-hours posttreatment, with a steady decline to less than 20% at 72-hours. In contrast, the effect of CAP on the viability of NHA and HUVEC was minimal, and importantly not significant at 90 to 120 seconds, with up to 85% of the cells remained viable at 72-hours post-treatment. CAP treatment produces both cytotoxic and apoptotic effects with some variability between cell lines. CAP treatment resulted in a G2/M-phase cell cycle pause in all three cell lines.ConclusionsThis preliminary study determined a multi-focal effect of CAP on glioma cells in vitro, which was not observed in the non-tumor cell lines. The decreased viability depended on the treatment duration and cell line, but overall was explained by the induction of cytotoxicity, apoptosis, and G2/M pause. Future studies will aim at further characterization with more complex pre-clinical models.

Cold atmospheric plasma treatment of melanoma and glioblastoma cancer cells

“…The cell viability was significantly lower 72 h following treatment compared to 24 h ( p < 0.05), which has also been observed with U87 by others . Cheng et al explain this effect by the generation of peroxynitrite in the medium after the plasma treatment has finished .…”

“…Effective treatment times in literature are generally shorter than observed in our study, i.e., between 1 and 3 min . The numerous parameters involved in experimental plasma medicine may each alone or in combination offer explanations to this observation, as well as to the variation encountered between replicates.…”

“…Therefore, the increasing RONS concentration can be used as an effective and selective treatment against cancer. Indeed, CAPs have been demonstrated to selectively induce cell death in cancer cells compared to normal cells …”

Plasma applications in medicine and dentistry

“…Utjecaj tretmana CAP-om na stanice tumora intenzivno se istražuje, što je rezultiralo velikim brojem studija u kojima su korišteni različiti izvori CAP-a i mnogobrojne stanič-ne linije izvedene iz različitih tumorskih tkiva 42,43 . Iako mehanizmi učinka tretmana CAP-om na stanice tumora još uvijek nisu u potpunosti razjašnjeni, treba istaknuti nekoliko osnovnih zaključaka/rezultata dosadašnjih studija: 1. tretman CAP-om rezultira povećanom koncentracijom intracelularnih ROS [50][51][52][53] . U tablici 1 prikazani su osnovni rezultati odabranih in vitro studija na humanim tumorima.…”

Cold atmospheric pressure plasma for treatment of chronic wounds: drug or medical device?

“…[9][10][11][12][13] First reports on the use of argon plasma for tumor removal date back to 1989 14 , followed by successful ablation of nonneoplastic Barrett's mucosa 15 and other neoplastic diseases. [16][17][18][19][20][21] A plasma-activated medium has even been claimed to exert anti-tumor effects. 22,23 Results of in-vitro, 24 in-vivo [24][25][26][27][28] and initial clinical studies on chronic wounds of domestic animals 29,30 and humans [31][32][33][34][35] indicate that CAP may be a promising alternative to conventional treatment options, based on the following biological premises:…”