Cold Atmospheric Plasma (CAP) is an ionized gas with a near room temperature. CAP is a controllable source for reactive species, neutral particles, electromagnetic field and UV radiation. CAP showed the promising application in cancer treatment through the demonstration in vitro and in vivo. In this study, we first demonstrate the existence of an activation state on the CAP-treated cancer cells, which drastically decreases the threshold of cell vulnerability to the cytotoxicity of the CAP-originated reactive species such as H2O2 and NO2−. The cytotoxicity of CAP treatment is still dependent on the CAP-originated reactive species. The activation state of cancer cells will not cause noticeable cytotoxicity. This activation is an instantaneous process, started even just 2 s after the CAP treatment begins. The noticeable activation on the cancer cells starts 10–20 s during the CAP treatment. In contrast, the de-sensitization of activation takes 5 hours after the CAP treatment. The CAP-based cell activation explains the mechanism by which direct CAP treatment causes a much stronger cytotoxicity over the cancer cells compared with an indirect CAP treatment do, which is a key to understand what the effect of CAP on cancer cells.
Cold atmospheric plasma (CAP) has shown strong anti-cancer capability in vitro and in vivo. The interaction between CAP and cancer cells build the foundation to understand the anticancer effect of a direct CAP treatment. The CAP-based activation phenomenon is a key factor to understand the CAP cancer treatment. The CAP-treated pancreatic adenocarcinoma cells instantaneously entered a specific activation state, in which these cancer cells become very sensitive to the cytotoxicity of both reactive oxygen species and reactive nitrogen species. Here, we present a roadmap of control the basic operational parameters of the CAP jet (the helium flow rate, the discharge voltage, and the discharge frequency) on the activation. Among three parameters, the discharge voltage shows the largest impact on the activation phenomenon. The maximum activation effect occurred when the discharge voltage reached a medium level. A 0D chemical simulation revealed that such maximum activation effect may be due to the maximum densities of several short-lived reactive species in CAP jet at a certain level of discharge voltage.
Understanding the interaction between cold atmospheric plasma (CAP) and cells is a critical challenge in plasma medicine. CAP has shown promising application for cancer treatment. To date, dozens of cancer cells have been selectively killed during in vitro studies, and CAP-originated reactive species have been regarded to be the primary factor causing cancer cell death. In the past, we investigated hydrogen peroxide (H 2 O 2) generation at the micromolar level using two CAP-treated cancer cell lines. In this study, we further demonstrate the universality of such strong cell-based H 2 O 2 generation in eight cancer cell lines. Nearly all lines showed capacity to generate a micromolar level of H 2 O 2 during 1 min of CAP treatment when discharge voltage (peak value) was > 3.30 kV. Generally, higher discharge voltage corresponds to stronger cell-based H 2 O 2 generation, although some cell lines produce maximum H 2 O 2 generation at relatively low discharge voltage. Cell-based H 2 O 2 generation may involve interaction between cancer cells and reactive oxygen species in CAP. The CAP (OH) radicals in CAP when discharge voltage is > 3.30 kV. This study demonstrates the universality of cell-based H 2 O 2 generation that has not been considered in previous studies.
Cancer treatment is a challenge in modern medicine. Several novel modalities have been invented to selectively treat cancer cells. The reactive species such as reactive oxygen species and reactive nitrogen species play important role in the anti-cancer capacity of several modalities, such as cold atmospheric plasma. In this study, we first demonstrated that a nanosecond-pulsed magnetic field (NMF) generator could sensitize the melanoma cell line B16-F10 to the cytotoxicity of an important ROS, H2O2. The magnetic field strength and the frequency were two key factors to control the activation level of NMF treatment. This study provided a novel strategy to use electromagnetic modality in cancer treatment particularly for the treatment on deep tumors such as brain, pancreatic, etc.
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