Bax, Bcl-2, and NF-kappaB expression in sanguinarine induced bimodal cell death.
The apoptosis related proteins Bax, Bcl-2, and NF-kappaB were analyzed in sanguinarine induced apoptosis and blister cell death (BCD) of K562 erythroleukemia cells and in sanguinarine treated high Bcl-2 expressing JM1 pre-B lymphoblastic cells, utilizing immunofluorescence-flow cytometry. Sanguinarine induced apoptosis of K562 cells was found to have increased Bax expression and decreased NF-kappaB, whereas BCD showed a decrease in Bax expression and an increase in NF-kappaB. In contrast, high Bcl-2 expressing JM1 cells, when exposed to the same concentrations (and duration) of sanguinarine that induced PCD and BCD in K562 cells, failed to show the respective morphologies while showing a concomitant increase in Bcl-2. Results from studies with K562 cells suggest that Bax is pro-apoptotic and also that NF-kappaB activation may be associated with BCD. Results from studies with JM1 cells suggest that Bcl-2 is anti-apoptotic and anti-BCD. Results from JM1 cells strengthen the assumption in the literature of the central role Bcl-2 plays in chemoresistance by assuming an anti-PCD role. These results also suggest that, in JM1 cells, Bcl-2 may further complicate chemoresistance by being anti-BCD in nature, in addition to its anti-PCD role.
Weerasinghe
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Faculty of Medicine, Memorial University of Newfoundland, 300 Prince Phillip Drive, St. John's, Newfoundland, A1B 3V6, Canada.
Hallock
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Liepins
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D000470:Alkaloids / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001402:B-Lymphocytes; D053119:Benzophenanthridines; D016923:Cell Death / Q000187:drug effects / Q000502:physiology*; D002467:Cell Nucleus / Q000187:drug effects / Q000648:ultrastructure; D002843:Chromatin / Q000187:drug effects / Q000648:ultrastructure; D005434:Flow Cytometry; D006801:Humans; D007546:Isoquinolines; D020014:K562 Cells; D016328:NF-kappa B / Q000032:analysis / Q000378:metabolism*; D010617:Phenanthridines / Q000494:pharmacology; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis / Q000378:metabolism*; D051028:bcl-2-Associated X Protein
D000470:Alkaloids; C494826:BAX protein, human; D053119:Benzophenanthridines; D002843:Chromatin; D007546:Isoquinolines; D016328:NF-kappa B; D010617:Phenanthridines; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C005705:sanguinarine