This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Regulation of Apoptosis in Cancer Cells Our studies show that MK-886, a known inhibitor of five lipoxygenase activating protein (FLAP) and also an inhibitor of peroxisome proliferator activated receptor alpha (PPAR?), induces apoptosis in CRL-2610 glioma cells and the breast adenocarcinoma MCF-7. Apoptosis was demonstrated by nuclear condensation, by nucleosome/histone release from the nucleus into the cytoplasm, by DNA laddering, and by annexin binding. FACS analysis demonstrated no necrosis as measured by the lack of uptake of propidium iodide, while there was a shift in the intensity of the emissions of the mitochondria associated Mito Tracker fluorescent probe. Our unpublished studies demonstrate for the first time that CRL-2610 cells express very low, if any, 12-lipoxygenase (12-Lox P or 12-Lox-B) mRNA, while MCF-7 cells express significant levels of both of these mRNAs. Furthermore, we show that CDC, a 12-Lox inhibitor, induces apoptosis in MCF-7 cells, but not in CRL-2610 cells. On the other hand, CRL-2610 cells are much more sensitive to apoptosis induced by MK886, relative to MCF-7 cells. Another finding we believe to be significant is that upon induction of apoptosis by MK886 there is a precipitous drop in the steady-state expression of c-myb, vinculin, and cadherin1 in CRL-2610 cells, but not in MCF-7 cells. Also of interest is that upon the induction of apoptosis by MK886 there was a precipitous drop in the expression of ALOX-E3 in MCF-7 cells, but not in CRL-2610 cells. The data presented here and the inherent differences in the cells indicate that a comparative study of MCF-7 and CRL-2610 cells could provide a unique model in which to obtain important information about the regulation of apoptosis in cancer cells.
Showing the most recent 10 out of 199 publications
