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. 2019 Sep 26;9:13931. doi: 10.1038/s41598-019-50329-3

Figure 5.

Figure 5

The principle of bystander signaling between tumor cells with inactivated catalase and untreated tumor cells. (A) The principle. Left side: In a mixture between tumor cells with inactivated membrane-associated catalase and untreated tumor cells the final percentage of apoptotic cells would be strictly correlated to the percentage of pretreated cells in the population. Right side: Experimental evidence has been provided60,95,96 that tumor cells with inactivated catalase drive a singlet oxygen-mediated bystander signaling that causes inactivation of membrane-associated catalase, reactivation of intercellular RONS signaling and apoptosis induction. As a result, the percentages of apoptotic cells are much higher than to be expected from the percentage of pretreated cells in the mixedpopulation. (B) Quantitative analysis of bystander signaling. The percentage of apoptotic cells is much higher than the percentage of pretreated cells with inactivated catalase, when bystander signaling is effective. Inhibition of bystander signaling leads to percentages of apoptotic cells that strictly correlate with the percentages of pretreated cells. This system allows analysis of the underlying molecular mechanisms through application of defined inhibitors or scavengers at distince steps. It also allows to determine the percentage of bystander-inducing cells in a population through titration of cells from this population on untreated cells and determining the percentage of apoptotic cells. If the induction of bystander inducing potential is a rare effect, a large portion of a cell population will be needed to induce bystander signaling, whereas a population with a high percentage of bystander effect-inducing cells will allow bystander induction even with a low percentage of these cells within an untreated population.