Toward understanding the selective anticancer capacity of cold atmospheric plasma—A model based on aquaporins (Review)

Abstract

Selectively treating tumor cells is the ongoing challenge of modern cancer therapy. Recently, cold atmospheric plasma (CAP), a near room-temperature ionized gas, has been demonstrated to exhibit selective anticancer behavior. However, the mechanism governing such selectivity is still largely unknown. In this review, the authors first summarize the progress that has been made applying CAP as a selective tool for cancer treatment. Then, the key role of aquaporins in the H2O2 transmembrane diffusion is discussed. Finally, a novel model, based on the expression of aquaporins, is proposed to explain why cancer cells respond to CAP treatment with a greater rise in reactive oxygen species than homologous normal cells. Cancer cells tend to express more aquaporins on their cytoplasmic membranes, which may cause the H2O2 uptake speed in cancer cells to be faster than in normal cells. As a result, CAP treatment kills cancer cells more easily than normal cells. Our preliminary observations indicated that glioblastoma cells consumed H2O2 much faster than did astrocytes in either the CAP-treated or H2O2-rich media, which supported the selective model based on aquaporins.

A Comparison of Floating-Electrode DBD and kINPen Jet: Plasma Parameters to Achieve Similar Growth Reduction in Colon Cancer Cells Under Standardized Conditions

“…As 200 ll of liquid on top of cells fully abrogated DBD plasma toxicity, these effectors may be for instance poration, UV-radiation, charged particles or short-lived species being decomposed in absence of target cells. For example, the DBD plasma may create nanopores [78] allowing the entry of species into cells by a process similar to aquaporins [79], a route potentially counteracted by excess liquid. Also, short wavelength UV radiation is efficiently scavenged by a few hundred nanometers of liquid layer [80].…”

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

“…Significant rise of intracellular ROS is the most common response of the CAP-treated cells [119] including cancer cells [18, 120], normal untransformed mammalian cells [5, 18], and yeast cells [34]. Oxidant-sensitive fluorescent dye 2,7-dichlorodihydrofluorescein diacetate (H 2 DCFDA) is the most common intracellular ROS probes in this field [17, 22, 27, 56, 71, 120].…”

“…However, most apoptosis pathways observed in the CAP-treated cancer cells is based on the mitochondrial pathway triggered by DNA damage and mitochondrial damage. DNA damage has been commonly observed as an early stage event upon the CAP treatment [44, 119]. DSB is the main damage style [27, 36, 64].…”

“…Among them, the cleavage of poly ADP-ribose polymerase (PARP) is an important early molecular marker of apoptosis [138]. Apoptosis is the main type of cancer cell death following the CAP treatment [43, 44, 119]. In the CAP-treated cancer cells, the release of cytochrome c into cytosol [38], the expression of NOXA [141], Bax [142], caspase-9 [143], caspase-3/7 [38, 47, 62, 130], the cleavage of PARP [31, 64], the loss of mitochondrial transmembrane potential [33, 38, 62, 96, 120], as well as DNA fragmentation [60] have been commonly observed.…”

Therapeutic Approaches Based on Plasmas and Nanoparticles

“…Combining these species in various controlled blends provides an unprecedented possibility to activate specific signaling pathways in cells and tissue. This is critical in fields such as cancer therapeutics in which introduction and delivery of these potentially selective highly reactive species into tumors would enable selective removal of cancer cells, while sparing healthy tissue [11,12].…”