title: Position of STAT-1 alpha in cycloheximide-dependent apoptosis triggered by TNF-alpha in human colorectal COLO 205 cancer cell line; role of polyphenolic compounds.
abstract: "Immune escape" is a crucial instrument used by carcinoma cells to overcome numerous strategies of immune system to delete transformed cells. Cellular factors that make cancer cells immune to defence mechanisms are incompletely understood while some remain ambiguous. Up to date evidence points to some proteins and/or signaling molecules that might be a basis for unusual behavior of cancer cells. In particular STAT kinases are currently in the main focus of attention since they were both shown to accelerate and/or to inhibit apoptosis. In our studies we observed that human colorectal COLO 205 cancer cells were resistant to TNF-alpha- or cycloheximide-induced cytotoxicity. However, when TNF-alpha (10 ng/ml) has been given along with cycloheximide (5 micro g/ml, CHX) COLO 205 cells died extensively from apoptosis. Apparently, cycloheximide sensitized cells to TNF-alpha-induced programmed cell death. To investigate the role of STAT-1 alpha in CHX-mediated TNF-alpha-induced COLO 205 cell death certain polyphenolic compounds were studied if they modulate STAT-1 alpha phosphorylation status and STAT-1 alpha-protein interaction at the level of TNF-alpha signalosome in the 6(th), 12(th), and 24(th) hour of experiment. Neither of phenolic compound, namely PI-3K inhibitor (LY294002, 20 microM) nor MEK inhibitor (PD98059, 50 microM), nor flavonol quercetin or kaempferol (10, 100 microM) in contrast to apigenin (20 microM) influenced COLO 205 cell viability during individual or combined treatment with TNF-alpha and CHX. We conclude, that some antiapoptotic proteins were involved but not STAT-1 alpha kinase to resist TNF-alpha-dependent cell death promoting activity. Summing up, except apigenin, the above-mentioned polyphenolic compounds were unable to modulate survival signal in COLO 205 cells initially believed to be suppressed by STAT-1 alpha.
authors.affiliation: Department of Physiological Sciences, Faculty of Veterinary Medicine, Warsaw Agricultural University, Warsaw, Poland.
authors.forename: B
authors.initials: B
authors.lastname: Pajak
authors.forename: B
authors.initials: B
authors.lastname: Gajkowska
authors.forename: A
authors.initials: A
authors.lastname: Orzechowski
mesh_terms: D047310:Apigenin / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D003513:Cycloheximide / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D050832:Interferon-Stimulated Gene Factor 3 / Q000378:metabolism*; D044949:Kaempferols / Q000494:pharmacology; D008024:Ligands; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D010636:Phenols / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D059808:Polyphenols; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D011794:Quercetin / Q000494:pharmacology; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors; D019139:Tumor Escape; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D047310:Apigenin; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D002867:Chromones; D003513:Cycloheximide; D005419:Flavonoids; D050832:Interferon-Stimulated Gene Factor 3; D044949:Kaempferols; D008024:Ligands; D020930:MAP Kinase Kinase Kinases; D009025:Morpholines; D010636:Phenols; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D059808:Polyphenols; D047428:Protein Kinase Inhibitors; D011500:Protein Synthesis Inhibitors; D011794:Quercetin; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha; C079868:gamma interferon activation factor; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C006552:kaempferol; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one