Position of STAT-1alpha in cycloheximide-dependent apoptosis triggered by TNF-alpha in human colorectal COLO 205 cancer cell line: role of polyphenolic compounds

• Autorzy: Pajak B. , Gajkowska B. , Orzechowski A.
• Języki publikacji: EN

Abstrakty

EN

“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 focuse 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 µg/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-1alpha in CHX-mediated TNF-alpha-induced COLO 205 cell death certain polyphenolic compounds were studied if they modulate STAT-1alpha phosphorylation status and STAT-1alpha-protein interaction at the level of TNF-alpha signalosome in the 6th, 12th, and 24th hour of experiment. Neither of phenolic compound, namely PI-3K inhibitor (LY294002, 20 µM) nor MEK inhibitor (PD98059, 50 µM), nor flavonol quercetin or kaempferol (10, 100 µM) in contrast to apigenin (20 µM) 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-1alpha kinase to resist TNF-alpha-dependent cell death promoting activity. Summing up, except apigenin, the above-mentioned polyphenolic componds were unable to modulate survival signal in COLO 205 cells initially believed to be suppressed by STAT-1alpha.

Słowa kluczowe

EN

polyphenolic compound; cell line; cycloheximide; STAT-1alpha position; tumour necrosis factor-alpha; COLO 205 colorectal cell; colorectal cancer; carcinoma cell; apoptosis; polyphenol; immune system

• Wydawca: -
• Czasopismo: Journal of Physiology and Pharmacology. Supplement
• Rocznik: 2005
• Tom: 56
• Numer: 3
• Opis fizyczny: p.119-141,fig.,ref.

Twórcy

autor

Pajak B.

• Warsaw Agricultural University, Nowoursynowska 159, 02-776 Warsaw, Poland

autor

Gajkowska B.

autor

Orzechowski A.