Evaluation of the anticancer effects induced by cold atmospheric plasma in 2D and 3D cell‐culture models

Abstract

The biological characteristics of three‐dimensional (3D) tumors cannot be adequately represented through two‐dimensional (2D) cell cultures. Here, to acquire more precise information about plasma–tumor interactions, the plasma‐induced cytotoxicity was tested in both 2D cell culture and 3D tumor‐spheroid culture. The results indicated that the toxic effects were markedly reduced in 3D cancer cells compared with 2D cells. We found that reactive oxygen and nitrogen species can penetrate through the entire depth of 3D tumor spheroid, but local apoptosis was observed only on the outermost layer. The permeation depth of plasma‐generated reactive species was then tracked in 3D tumor spheroids. We hypothesized that plasma‐induced apoptosis within a tumor depends on the “deep” delivery of H2O2, NO2−, and NO3− rather than O2−, OH•, and ONOOH/ONOO−.

Plasma induced reactive oxygen species‐dependent cytotoxicity in glioblastoma 3D tumourspheres

“…It was reported that despite the ability of RONS to penetrate throughout the entire depth of 3D tumourspheroids, apoptosis was observed only on the outermost layer or surface. [9] However, this is not what occurs in our case. We used confocal microscopy alongside a 3D reconstruction of stacked images to build three-dimensional maps of the treated tumourspheres.…”

“…[5,6] Devices that generate CAP can be divided into: direct-discharge (i.e., dielectric barrier discharge (DBD), pin to plate system) and indirect-discharge (i.e., plasma jets, pens, and torches). [5,7] CAP-induced cancer cellular cytotoxicity has been demonstrated previously by using different devices, such as plasma jet, [8][9][10][11][12] micro-sized devices, [13] DBDs [14,15], and corona discharges. Previous studies have reported both direct and indirect CAP treatment efficacies in inducing anticancer effects (in numerous cancer types, such as pancreatic, [8] lung, [9,10] squamous cell carcinoma, [11] brain, [13] and so forth) in in vitro [8,9,11] and antitumor effects in vivo.…”

“…[5,7] CAP-induced cancer cellular cytotoxicity has been demonstrated previously by using different devices, such as plasma jet, [8][9][10][11][12] micro-sized devices, [13] DBDs [14,15], and corona discharges. Previous studies have reported both direct and indirect CAP treatment efficacies in inducing anticancer effects (in numerous cancer types, such as pancreatic, [8] lung, [9,10] squamous cell carcinoma, [11] brain, [13] and so forth) in in vitro [8,9,11] and antitumor effects in vivo. [11][12][13] Increasingly CAP is being explored as a novel therapeutic method for cancer treatment due to the fact that it operates at atmospheric pressure and near room temperature while having low power requirements.…”

The Antitumor Effects of Plasma-Activated Saline on Muscle-Invasive Bladder Cancer Cells In Vitro and In Vivo Demonstrate Its Feasibility as a Potential Therapeutic Approach

“…The contents of aqueous O 2 − /ONOO − /ONOOH were measured using the TEMPONE-H (1-hydroxy-2,2,6,6-tetramethyl-4-oxo-piper-idine, Enzo, 5 mM). Detailed ROS and RNS detection methods are outlined in our previous paper [ 45 ]. PAS sampling for H 2 O 2 , NO 2 − and NO 3 − measurement were completed within 5 min after plasma irradiation due to other operations.…”

Study of the anticancer effects of a helium plasma jet combined with four anticancer drugs on 3D bladder tumour spheroids

“…In this paper, based on three-dimensional (3D) T24 bladder tumour spheroids (which more accurately mimic the biological characteristics of cancer cells in vivo than other models), [14,15] the anticancer effects of a helium atmospheric pressure plasma jet combined with four commonly used clinical antibladder cancer drugs (cisplatin, methotrexate, adriamycin and paclitaxel) were tested. The effects of these four drugs on the global ROS levels in the medium of the plasma jet-treated spheroids were analysed by detecting the oxidation-reduction potential (ORP).…”