In @entity1 panc-1 @entity788 cells, @entity4316 (act D) induces a type 1 (apoptotic, extrinsic, death domain, receptor-dependent, and caspase-positive) form of @entity204 ( @entity204 ) and @entity20463 , a 5-lipoxygenase inhibitor serving among other functions as a surrogate for increasing oxidative stress, a type 2 form, defined as an intrinsic, mitochondria-dependent, autophagic form of cellular suicide. Using both agents simultaneously should allow for examination of their interaction in cells able to express either form of @entity204 . Activation of both forms might result in synergistic, additive, null, or inhibitory effects on the reduction in proliferation, @entity204 , and clonogenicity of surviving cells. Co-culture of panc-1 cells with act D and @entity20463 , which both inhibit their proliferation, had an additive effect on increasing the development of these forms of @entity204 , as determined by morphology, a nucleosome assay, and flow cytometry. Initially, laddering on agarose detected with @entity2667 , present in act D, and act D plus @entity20463 -treated cells was partially obscured by randomly degraded DNA. With the use of the more sensitive SYBR green dye and reduced exposure of detached cells to 37 degrees C, a limited laddering of DNA from @entity20463 -treated cells was also detected. Caspase activity was present in act-D-cultured cells but was absent in cells cultured with @entity20463 . Combined culture reduced caspase activity in act D-treated cells, consistent with interference from type 2 of type 1 @entity204 . Removal after 48 hr of act D or @entity20463 allowed regrowth of residual cells, the latter agent to a greater extent than the former. In combination, the number of clones was increased compared with act D alone. These features distinguish two forms of @entity204 . In therapeutic settings in which the modes of cell death have not been identified, unintentional activation of several cellular suicide pathways with "crosstalk" between them occurs. Their intentional simultaneous activation and responses, as modulated by the history of cells in or out of cycle, could reduce the intended therapeutic outcome with survival of additional clonogenic cells due to various forms of mutual interference.

Caspase-dependent and -independent panc-1 cell death due to @entity4316 and XXXX are additive but increase clonogenic survival.

@entity1 :: ('9606', 'Species') :: ['human'] @entity788 :: ('MESH:D010190', 'Disease') :: ['pancreatic cancer'] @entity20463 :: ('MESH:C060893', 'Chemical') :: ['MK 886'] @entity2667 :: ('MESH:D011419', 'Chemical') :: ['propidium iodide'] @entity4316 :: ('MESH:D003609', 'Chemical') :: ['actinomycin D'] @entity204 :: ('MESH:D003643', 'Disease') :: ['PCD', 'programmed cell death']
@entity20463 :: (MESH:C060893,Chemical) :: ['MK 886']
