The role of aquaporins in the anti-glioblastoma capacity of the cold plasma-stimulated medium

Abstract

The cold atmospheric plasma (CAP) is a promising novel anti-cancer method. Our previous study showed that the cold plasma-stimulated medium (PSM) exerted remarkable anti-cancer effect as effectively as the direct CAP treatment did. H 2 O 2 has been identified as a key anticancer substance in PSM. However, the mechanisms underlying intracellular H 2 O 2 regulation by cancer cells is largely unknown. Aquaporins (AQPs) are the confirmed membrane channels of H 2 O 2 . In this study, we first demonstrated that the anti-glioblastoma capacity of PSM could be inhibited by silencing the expression of AQP8 in glioblastoma cells (U87MG) or using the aquaporins-blocker silver atoms. This discovery illustrates the key intermediate role of AQPs in the toxicity of PSM on cancer cells. Because the expression of AQPs varies significantly among different cancer cell lines, this study may facilitate the understanding on the diverse responses of cancer cells to PSM or the direct CAP treatment.

New Hopes for Plasma-Based Cancer Treatment

“…In glioblastoma cells, down-regulation of survival and proliferation signaling networks plays a critical role in PAM-induced apoptosis [9,42,44]. Aquaporins, which transport hydrogen peroxide into the plasma membrane, are also key factors in apoptosis induction [45]. Many in vivo experiments have also demonstrated the anti-tumor effects of PAM against a variety of cancers.…”

Direct plasma stimuli including electrostimulation and OH radical induce transient increase in intracellular Ca2+ and uptake of a middle‐size membrane‐impermeable molecule

“…We experimentally showed that relatively short‐lived reactive species (i.e., deactivated within approximately 10 min) in APP‐irradiated solution could activate transient receptor potential (TRP) channel family member(s) and induce physiologically relevant calcium (Ca 2+ ) influx, which plays key roles in many cellular processes . Regarding APP‐induced anti‐cancer effects, Yan et al reported that knockdown of aquaporin‐8 significantly inhibited the anti‐cancer capacity of APP‐irradiated medium . These reports indicate that membrane transporters, channels, and membrane receptors mediate between reactive species in APP‐irradiated solution and the evoked cellular responses, and thus are important biological target of APP‐produced reactive species.…”

“…[10] Regarding APPinduced anti-cancer effects, Yan et al reported that knockdown of aquaporin-8 significantly inhibited the anti-cancer capacity of APP-irradiated medium. [11] These reports indicate that membrane transporters, channels, and membrane receptors mediate between reactive species in APP-irradiated solution and the evoked cellular responses, and thus are important biological target of APP-produced reactive species.…”

Cold Atmospheric Plasma: A Powerful Tool for Modern Medicine

“…CAP-activated media generally induce apoptosis due to ROS, RNS, and H 2 O 2 content [147]. The resultant effect, however, may be cell-specific and dependent on parameters such as the amount of aquaporins in the cell line [148].…”