Induction of apoptosis and NF-kappaB by quercetin in growing murine L1210 lymphocytic leukaemic cells potentiated by TNF-alpha.
Polyphenol quercetin induced apoptosis in proliferating murine L1210 lymphocytic cells. DNA damage, as well as apoptosis and withdrawal from the cell cycle were transient. The above mentioned death promoting activity of quercetin was enhanced by physiological concentrations of TNF-alpha. At the same time, indices of cell viability dropped. However, the extent and tendency of the initially enhanced cell mortality steadily diminished throughout the experiment. After 12 h the G2/M phase reappeared. After 24 h all indices almost returned to control levels indicating either the selection of subpopulation of unaffected leukaemic cells or cells developing resistance to the treatment. A DNA ladder of oligonucleosomes was observed for apoptogenic treatments. We conclude that quercetin unmasked cell death, promoting the activity of TNF-alpha. However, after 12 and 24 h of exposure, surviving cells could complete the cell cycle and finally recover. At the same time, increased NF-kappaB activation was demonstrated by immunoblotting of the immunoreactive RelA/p65 subunit in nuclear extracts. Exposure to TNF-alpha or quercetin was crucial for increased activity of NF-kappaB, which may implicate an increasing resistance to their cytotoxicity.
Orzechowski
A
A
Department of Physiology, Biochemistry, Pharmacology and Toxicology, Faculty of Veterinary Medicine, Warsaw Agricultural University, Poland. orzechowski@alpha.sggw.waw.pl
Grzelkowska
K
K
Zimowska
W
W
Skierski
J
J
Ploszaj
T
T
Bachanek
K
K
Motyl
T
T
Karlik
W
W
Filipecki
M
M
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage; D053938:DNA Fragmentation; D004587:Electrophoresis, Agar Gel; D005434:Flow Cytometry; D015151:Immunoblotting; D007700:Kinetics; D007939:Leukemia L1210 / Q000473:pathology*; D051379:Mice; D016328:NF-kappa B / Q000187:drug effects* / Q000378:metabolism; D011794:Quercetin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D011794:Quercetin