Reactive species in non-equilibrium atmospheric-pressure plasmas: Generation, transport, and biological effects

// Dayun Yan 1 , Jonathan H. Sherman 2 and Michael Keidar 1 1 Department of Mechanical and Aerospace Engineering, The George Washington University, NW, Washington, DC, USA 2 Neurological Surgery, The George Washington University, NW, Washington, DC, USA Correspondence to: Dayun Yan, email: // Michael Keidar, email: // Keywords : cold plasma, cancer treatment, reactive species, selectivity Received : September 14, 2016 Accepted : October 29, 2016 Published : November 11, 2016 Abstract Over the past decade, cold atmospheric plasma (CAP), a near room temperature ionized gas has shown its promising application in cancer therapy. Two CAP devices, namely dielectric barrier discharge and plasma jet, show significantly anti-cancer capacity over dozens of cancer cell lines in vitro and several subcutaneous xenograft tumors in vivo. In contrast to conventional anti-cancer approaches and drugs, CAP is a selective anti-cancer treatment modality. Thus far establishing the chemical and molecular mechanism of the anti-cancer capacity of CAP is far from complete. In this review, we provide a comprehensive introduction of the basics of CAP, state of the art research in this field, the primary challenges, and future directions to cancer biologists.

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Cold atmospheric plasma, a novel promising anti-cancer treatment modality.

Purpose 
Nonequilibrium atmospheric pressure plasma (NEAPP) therapy has recently been focused on as a novel medical practice. Using cells with acquired paclitaxel/cisplatin resistance, we elucidated effects of indirect NEAPP-activated medium (NEAPP-AM) exposure on cell viability and tumor growth in vitro and in vivo.


Methods 
Using chronic paclitaxel/cisplatin-resistant ovarian cancer cells, we applied indirect NEAPP-exposed medium to cells and xenografted tumors in a mouse model. Furthermore, we examined the role of reactive oxygen species (ROS) or their scavengers in the above-mentioned EOC cells.


Results 
We assessed the viability of NOS2 and NOS3 cells exposed to NEAPP-AM, which was prepared beforehand by irradiation with NEAPP for the indicated time. In NOS2 cells, viability decreased by approximately 30% after NEAPP-AM 120-sec treatment (P<0.01). The growth-inhibitory effects of NEAPP-AM were completely inhibited by N-acetyl cysteine treatment, while L-buthionine-[S, R]-sulfoximine, an inhibitor of the ROS scavenger used with NEAPP-AM, decreased cell viability by 85% after NEAPP-AM 60-sec treatment(P<0.05) and by 52% after 120 sec, compared to the control (P<0.01). In the murine subcutaneous tumor-formation model, NEAPP-AM injection resulted in an average inhibition of the NOS2 cell-inoculated tumor by 66% (P<0.05) and NOS2TR cell-inoculated tumor by 52% (P<0.05), as compared with the control.


Conclusion 
We demonstrated that plasma-activated medium also had an anti-tumor effect on chemo-resistant cells in vitro and in vivo. Indirect plasma therapy is a promising treatment option for EOC and may contribute to a better patient prognosis in the future.

https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0081576&type=printable

Effect of Indirect Nonequilibrium Atmospheric Pressure Plasma on Anti-Proliferative Activity against Chronic Chemo-Resistant Ovarian Cancer Cells In Vitro and In Vivo

Plasma medicine is a relatively new field that grew from research in application of low-temperature (or cold) atmospheric plasmas in bioengineering. One of the most promising applications of cold atmospheric plasma (CAP) is cancer therapy. Convincing evidence of CAP selectivity towards the cancer cells has been accumulated. This review summarizes the state of the art of this emerging field, presenting various aspects of CAP application in cancer such as the role of reactive species (reactive oxygen and nitrogen), cell cycle modification, in vivo application, CAP interaction with cancer cells in conjunction with nanoparticles, and computational oncology applied to CAP.

https://iopscience.iop.org/article/10.1088/0963-0252/24/3/033001/pdf

Plasma for cancer treatment

Plasma in cancer treatment

Two independent ovarian cancer cell lines and fibroblast controls were treated with nonequilibrium atmospheric pressure plasma (NEAPP). Most ovarian cancer cells were detached from the culture dish by continuous plasma treatment to a single spot on the dish. Next, the plasma source was applied over the whole dish using a robot arm. In vitro cell proliferation assays showed that plasma treatments significantly decreased proliferation rates of ovarian cancer cells compared to fibroblast cells. Flow cytometry and western blot analysis showed that plasma treatment of ovarian cancer cells induced apoptosis. NEAPP could be a promising tool for therapy for ovarian cancers.

Selective killing of ovarian cancer cells through induction of apoptosis by nonequilibrium atmospheric pressure plasma

Two independent ovarian cancer cell lines and fibroblast controls were treated with nonequilibrium atmospheric pressure plasma (NEAPP). Most ovarian cancer cells were detached from the culture dish by continuous plasma treatment to a single spot on the dish. Next, the plasma source was applied over the whole dish using a robot arm. In vitro cell proliferation assays showed that plasma treatments significantly decreased proliferation rates of ovarian cancer cells compared to fibroblast cells. FACS and Western blot analysis showed that plasma treatment of ovarian cancer cells induced apoptosis. NEAPP could be a promising tool for therapy for ovarian cancers.

https://www.cambridge.org/core/services/aop-cambridge-core/content/view/S194642741200927X

Moemi Hayashi

Papers

Selective killing of ovarian cancer cells through induction of apoptosis by nonequilibrium atmospheric pressure plasma

Selective Killing of Ovarian Cancer Cells through Induction of Apoptosis by a Nonequilibrium Atmospheric Pressure Plasma