Disparate forms of MK 886-induced programmed death in BCL-2 (+) blood and BCL-2 (-) solid cancer cells and a putative "nuclear" Ca2+ channel: "soil" trumps "seed"?
The five-lipoxygenase inhibitor, MK 886, in micromolar concentration induces a "type 1" form of programmed cell death in U937 human monoblastoid cells and a "type 2" form in Panc-1 pancreatic and PC3 prostate cell lines. The latter two lines originate from epithelial-derived solid human cancers. An acute rise in Ca(2+) occurs in U937 and HL 60 myeloid cells, in U937 cells located in their nuclei (HL 60 not tested), both of which are Bcl-2 positive. The two solid cancer cell lines express neither of these features. Solid tumor-derived Bcl-2-positive HeLa cervical cancer cells exhibit an acute increase in Ca(2+) after challenge with MK 886. In U937, PC3 and Panc-1 cells tested, the agent acutely increases oxidative stress and decreases mitochondrial membrane potential, indicating that neither event is directly determinative for the form of PCD. The role of mitochondria and the mechanism by which increased oxidative stress initiates the acute rise in U937 "nuclear" Ca(2+), the contribution, if any, of Bcl-2 in initiating the Ca(2+) signal and the latter in mandating the type of PCD, presumably through differential modulation of transcription, remain to be determined. Lastly, these results demonstrate that "soil" trumps "seed".


OBJECTIVE
Despite similarities in response, including those of the mitochondria to micromolar concentrations of MK 886, hematopoietic and epithelial-derived non-hematopoietic solid cancer cell lines exhibit dissimilar forms of programmed cell death. These differences may depend upon the presence of Bcl-2 or a related protein participating in a juxta-nuclear/nuclear Ca(2+) ion-channel. Evidence for this supposition is discussed.
Anderson
K M
KM
The Hektoen Institute, and Cook County Hospital, 2100 W Harrison, Chicago, IL 60612, USA. kanderso@rush.edu
Rubenstein
M
M
Tsui
P
P
Harris
J E
JE
D017209:Apoptosis / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D019254:Genes, bcl-2 / Q000235:genetics; D006801:Humans; D007211:Indoles / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D014407:Tumor Cells, Cultured; D002722:Chlorobenzenes
D002118:Calcium; D015220:Calcium Channels; D007211:Indoles; D019253:Proto-Oncogene Proteins c-bcl-2; C060893:MK-886; D002722:Chlorobenzenes