The actinomycin D-induced apoptosis in BCR-ABL-positive K562 cells is associated with cytoplasmic translocation and cleavage of RNA helicase A.
K562 cells express the fusion protein BCR-ABL and have been shown to be relatively more resistant to apoptosis induction by chemotherapeutic agents. We show that Actinomycin D (Act D) induces time- and dose-dependent apoptosis in K562 cells. Act D causes early activation of caspase-3 followed by inhibition of the expression of the anti-apoptotic proteins BCR-ABL and Bcl-xl. Act D-induced apoptosis is associated with cytoplasmic translocation and cleavage of the multifunctional nuclear protein RNA helicase A (RHA). RHA has roles in transcription and RNA metabolism and has been shown to be cleaved during Fas mediated apoptosis. These results suggest that Act D causes caspase-3 activation and apoptosis in BCR-ABL positive K562 cells and that RHA cytoplasmic translocation and cleavage occur in chemotherapy-induced apoptosis.
Abdelhaleem
Mohamed
M
Division of Haematopathology, Department of Paediatric Laboratory Medicine, Hospital for Sick Children, University of Toronto, Toronto, Canada. mohamed.abdelhaleem@sickkids.ca
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001324:Autoantigens / Q000378:metabolism*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D003593:Cytoplasm / Q000201:enzymology; D053487:DEAD-box RNA Helicases; D003609:Dactinomycin / Q000494:pharmacology*; D004789:Enzyme Activation; D005047:Etoposide / Q000494:pharmacology; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D006801:Humans; D020014:K562 Cells; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D020365:RNA Helicases / Q000378:metabolism*; D051020:bcl-X Protein
D000903:Antibiotics, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D001324:Autoantigens; C494811:BCL2L1 protein, human; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; D003609:Dactinomycin; D005047:Etoposide; D016044:Fusion Proteins, bcr-abl; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; C098487:DHX9 protein, human; D053487:DEAD-box RNA Helicases; D020365:RNA Helicases