Cancer treatment by cold atmospheric plasma (CAP) offers the possibility to selectively eliminate cancer cells while leaving surrounding, normal cells, unaffected. The mechanisms underlying the CAP selectivity towards cancer cells are yet not fully understood , but it has been proposed that two apoptosis-inducing signaling pathways in the extracellular compartment are reactivated when catalase in the cell membrane of cancer cells is inactivated. Since CAP has the capacity to inactivate catalase, CAP may thus be used to induce cancer cell death by reactivation of these signaling pathways. A better insight of this specific apoptosis-inducing mechanism - especially the role of catalase inactivation - could be useful to increase our understanding of possible roles of CAP constituents in cancer treatment . In the present study,  a mathematical model describing the reaction kinetics of the two apoptosis-inducing signaling pathways is developed and used to theoretically investigate their catalase-dependent reactivation. The results show that when only the reaction kinetics is considered, just one of the pathways may be responsible for apoptosis induction. This pathway requires a high catalase concentration (in the order of mM) to be inhibited, which thus can be assumed to be the condition of cancer cells before CAPtreatment, and it can only be reactivated by inactivation of about 99\% of the catalase. This model is a first step into the efforts that should be taken to quantitatively understand the complex mechanisms of the role of CAP and catalase in the apoptosis-inducing signaling pathways, but will need to be further extended before it can capture the entire mechanism. Still, it gives some important insights regarding necessary conditions in order for the proposed mechanism to represent a feasible explanation of selective CAP treatment of cancer cells .
Cold atmospheric plasma (CAP) is a promising new agent for (selective) cancer treatment, but the underlying cause of the anti-cancer effect of CAP is not well understood yet. Among different theories and observations, one theory in particular has been postulated in great detail and consists of a very complex network of reactions that are claimed to account for the anti-cancer effect of CAP. Here, the key concept is a reactivation of two specific apoptotic cell signaling pathways through catalase inactivation caused by CAP. Thus, it is postulated that the anti-cancer effect of CAP is due to its ability to inactivate catalase, either directly or indirectly. A theoretical investigation of the proposed theory, especially the role of catalase inactivation , can contribute to the understanding of the underlying cause of the anti-cancer effect of CAP . In the present study, we develop a mathematical model to analyze the proposed catalase-dependent anti-cancer effect of CAP. Our results show that a catalase-dependent reactivation of the two apoptotic pathways of interest is unlikely to contribute to the observed anti-cancer effect of CAP. Thus, we believe that other theories of the underlying cause should be considered and evaluated to gain knowledge about the principles of CAP-induced cancer cell death .
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Cancer treatment by cold
Cold
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offers the possibility to selectively eliminate cancer cells while leaving surrounding, normal cells, unaffected. The mechanisms underlying the
is a promising new agent for (selective) cancer treatment, but the underlying cause of the anti-cancer effect of CAP is not well understood yet. Among different theories and observations, one theory in particular has been postulated in great detail and consists of a very complex network of reactions that are claimed to account for the anti-cancer effect of CAP. Here, the key concept is a reactivation of two specific apoptotic cell signaling pathways through catalase inactivation caused by CAP. Thus, it is postulated that the anti-cancer effect of
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selectivity towards cancer cells are yet not fully understood , but it has been proposed that two apoptosis-inducing signaling pathways in the extracellular compartment are reactivated when catalase in the cell membrane of cancer cells is inactivated. Since CAP has the capacity to
is due to its ability to
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CAP may thus be used to induce cancer cell death by reactivation of these signaling pathways. A better insight of this specific apoptosis-inducing mechanism -
either directly or indirectly. A theoretical investigation of the proposed theory,
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- could be useful to increase our understanding of possible roles of CAP constituents in cancer treatment
, can contribute to the understanding of the underlying cause of the anti-cancer effect of CAP
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we develop
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describing the reaction kinetics of the two apoptosis-inducing signaling pathways is developed and used to theoretically investigate their
to analyze the proposed
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reactivation. The
anti-cancer effect of CAP. Our
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when only the reaction kinetics is considered, just one of the pathways may be responsible for apoptosis induction. This pathway requires a high catalase concentration (in the order of mM) to be inhibited, which thus can be assumed to be the condition of cancer cells before CAPtreatment, and it can only be reactivated by inactivation of about 99\% of the catalase. This model is a first step into the efforts that should be taken to quantitatively understand the complex mechanisms of the role of CAP and catalase in the apoptosis-inducing signaling pathways, but will need to be further extended before it can capture the entire mechanism. Still, it gives some important insights regarding necessary conditions in order for the proposed mechanism to represent a feasible explanation of selective CAP treatment of cancer cells
a catalase-dependent reactivation of the two apoptotic pathways of interest is unlikely to contribute to the observed anti-cancer effect of CAP. Thus, we believe that other theories of the underlying cause should be considered and evaluated to gain knowledge about the principles of CAP-induced cancer cell death