Cold atmospheric pressure plasma treatment combined with starvation increases autophagy and apoptosis in melanoma in vitro and in vivo

Abstract

Despite advances in therapy, malignant melanoma remains a fatal disease. Among several emerging approaches to combat cancer, cold atmospheric pressure plasma (CAP) has shown promising results as a novel antitumor agent in preclinical models so far. The technology mainly relies on the emittance of various reactive oxygen and nitrogen species (ROS/RNS) that are tumor-toxic at high concentrations. Moreover, malignant melanoma has a metabolic dimension that can be targeted by mild starvation.To this end, we investigated the combined effect of starvation and CAP treatment on melanoma in vitro and in vivo. In vitro, starvation+CAP led to cell morphology changes, decreased metabolic activity and increased lipid peroxidation accompanied by apoptosis and DNA fragmentation in murine B16 melanoma cells but not murine non-malignant L929 fibroblasts. This was paralleled by increased apoptosis (Bax, Bcl-2 and Caspase-3) and autophagy (Lc3 and Atg5)-related gene expression. In vivo, starvation reduced tumor burden. Combination with CAP treatment augmented this effect significantly, albeit there was no difference of combination treatment to CAP exposure alone. Interestingly, there was an overall greater increase of Lc3 and Atg5 in the tumor tissue compared to CAP exposure alone, while starvation-induced autophagy-related gene expression was similar to in the combination group. These data collectively suggest that CAP-derived ROS/RNS treatment and autophagy-induction augment antitumor effects in malignant melanoma in vitro and in vivo.

Cold Atmospheric Plasma Conveys Selectivity Against Hepatocellular Carcinoma Cells via Triggering EGFR(Tyr1068)-Mediated Autophagy

“…As autophagy has been lately shown to be capable of inhibiting cancer stemness in triple-negative breast cancers ( 28 ), and CAP was recently demonstrated with the attributes of triggering autophagy in melanoma cells ( 29 ); we examined whether and how CAP possibly could affect HCC cell autophagy.…”

Cold atmospheric plasma: Novel opportunities for tumor microenvironment targeting

“…Cold atmospheric plasma is composed of varied reactive oxygen and nitrogen species (RONS) including short‐lived species such as hydroxyl radical (OH·), singlet oxygen (O), superoxide (O 2− ), and nitric oxide (NO·), and long‐lived species such as hydrogen peroxide (H 2 O 2 ), ozone (O 3 ), anionic (OONO − ), and protonated (ONOOH) forms of peroxynitrite. Since the first discovery on the anti‐cancer efficacy of CAP in 2007, consecutive efforts have been devoted to investigate its onco‐therapeutic impacts in varied types of cancers with demonstrated efficacies already been proven in, for example, triple negative breast cancers, 201 bladder cancers, 202 prostate cancers, 203 melanomas, 204 and pancreatic cancers 205 . Differential cell death events can be triggered by CAP in a dose‐dependent manner 206 that include, for example, cell cycle arrest, 203 autophagy, 207 apoptosis, 201 ferroptosis, 208 immunogenic cell death (ICD), 209 and necrotic cell death 210 .…”

Autophagy and autophagy signaling in Epilepsy: possible role of autophagy activator

“…Growth factors like insulin-like growth factor (IGF) through activation of IGF receptors (IGFRs) promote the activity of tyrosine kinase and Aκt leading to activation of the mTOR pathway and inhibition of autophagy (Sepúlveda et al 2022 ). Mild starvation also inhibits the mTOR pathway, but the kinase activity remains unaffected leading to acceleration of fusion between the autophagosome and lysosomes (Golpour et al 2022 ). However, when the nutrients are replenished the mTOR pathway is inhibited with a significant reduction of autophagosomes (Golpour et al 2022 ).…”