Apoptosis induction by inhibitors of Ser/Thr phosphatases 1 and 2A is associated with transglutaminase activation in two different human epithelial tumour lines.
Two epithelial tumour lines, HeLa and KB, were treated with okadaic acid and calyculin A, specific inhibitors of Ser/Thr phosphatases (PP), esp. PP1 and PP2A. Morphological criteria, analysis of DNA fragmentation and studies of membrane integrity revealed that both agents concentration- and time-dependently induced apoptosis at nanomolar concentrations which in these cells was associated with the stimulation of a transglutaminase activity. Since a non-functional derivative of okadaic acid did not affect cell viability apoptosis was apparently related to the inhibition of PP1 and PP2A. Membrane damage marker activity was delayed by at least 24 h when compared to nuclear alterations.
von Zezschwitz
C
C
Institute of Pharmacology and Toxicology, University of Göttingen, Germany.
Vorwerk
H
H
Tergau
F
F
Steinfelder
H J
HJ
D017209:Apoptosis; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D004848:Epithelium / Q000187:drug effects / Q000201:enzymology / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008387:Marine Toxins; D019319:Okadaic Acid / Q000494:pharmacology; D010080:Oxazoles / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000502:physiology*; D013997:Time Factors; D011503:Transglutaminases / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D008387:Marine Toxins; D010080:Oxazoles; D019319:Okadaic Acid; C059041:calyculin A; D007770:L-Lactate Dehydrogenase; D011503:Transglutaminases; D010749:Phosphoprotein Phosphatases