Universality of Micromolar-Level Cell-Based Hydrogen Peroxide Generation during Direct Cold Atmospheric Plasma Treatment

Abstract

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.

Cold atmospheric plasma cancer treatment, direct versus indirect approaches

“…The singlet oxygen density in CAP was calculated based on the measurement of the optical emission spectrum of CAP under different discharge conditions. 104 The maximum density of O at the middle discharge voltage conditions has been observed in data based on OES. 104 The cells-based H 2 O 2 generation also provides a new clue to understanding the in vivo immune response of the CAP-treated mice.…”

“…104 The maximum density of O at the middle discharge voltage conditions has been observed in data based on OES. 104 The cells-based H 2 O 2 generation also provides a new clue to understanding the in vivo immune response of the CAP-treated mice. The short-lived reactive species such as superoxide or single oxygen may activate cancer cells or tissues to generate H 2 O 2 .…”

Direct cold atmospheric plasma and plasma‐activated medium effects on breast and cervix cancer cells

“…[ 51 ] Moreover, direct plasma produces higher H 2 O 2 compare to PAM after treatments (Figure 9), which shows the higher‐level impact of direct‐plasma treatment. Excess H 2 O 2 in direct‐plasma‐treated compared with PAM‐treated is due to the intracellular generation that has been previously demonstrated by Yan et al [ 58 ] They showed that different cancer cell lines had the capacity to generate H 2 O 2 by different discharge voltage of CAP. The results of the current study showed that the level of H 2 O 2 immediately after treatment with direct plasma was about 1.5‐fold higher than the PAM treatment.…”

“…It has been shown that the central reactive species in PAM should be mainly long‐lived, rather than short‐lived species. [ 58 ] Probably, the short‐lived species in He + 0.5% O 2 are more than He, but in the PAM method they cannot affect the cancer cells and just long‐lived species have an impact on cancer cells. This claim needs further investigation in future studies.…”

“…The amount of the cell‐based generation of H 2 O 2 was calculated by subtracting the concentration of H 2 O 2 in direct‐plasma and PAM treatment groups, as was done before, with just a few modifications. [ 58 ]…”