Apoptotic pathways of cell death induced by an interleukin-13 receptor-targeted recombinant cytotoxin in XXXX cells.

@entity1 @entity135 @entity137 @entity522 @entity4047 @entity588 @entity589 @entity5 @entity9596 @entity2455 @entity3542 @entity842 @entity9190
@entity9596 ( @entity9596 )-targeted cytotoxin, @entity4047 -PE38QQR, composed of @entity4047 and a mutated form of Pseudomonas exotoxin (PE), is found to be highly and specifically cytotoxic to @entity1 solid @entity5 cell lines. However, the mechanism of @entity5 cell death mediated by @entity4047 toxin is still not known. To elucidate the mechanism, we utilized four @entity135 cell lines (SCC-25, HN12, KCCT873, and YCUM911), which express high levels of @entity9596 , and @entity4047 toxin is highly cytotoxic to these cells. We observed chromatin condensation and DNA fragmentation, indicating apoptotic cell death, after treatment with @entity4047 toxin, as determined by @entity2455 staining and DNA ladder assays. However, @entity4047 did not induce cell death. Flow cytometric analysis suggested that these @entity5 cell lines increased the sub-G1/G0 phase DNA population in a dose- and time-dependent manner (ranged between 10 and 30%) after treatment with @entity4047 toxin. By Western blot analysis, cleavage of @entity522 and @entity9190 was observed after treatment with a high concentration of @entity4047 toxin, also suggesting apoptotic cell death. In addition, the results of immunofluorescence and RT-PCR assays showed that the apoptosis-regulator, @entity588 was downregulated after treatment with @entity4047 toxin, while @entity589 was upregulated. Moreover, significant @entity3542 production was detected in the HN12 cell line after treatment with @entity4047 toxin for 48--96 h. Taken together, our results suggest that @entity4047 toxin-induced @entity137 is at least partially mediated by the apoptosis and @entity842 pathways. This information may be useful in developing specific approaches where apoptotic bodies from @entity5 cells may be used to pulse antigen-presenting cells for immunotherapy of @entity5 .
