Sanguinarine induces bimodal cell death in K562 but not in high Bcl-2-expressing JM1 cells.
Our previous studies with low Bcl-2-expressing K562 cells have shown that, when treated with the putative anti-cancer drug sanguinarine, concentrations of 1.5 microg/ml induced the morphology of apoptosis or programmed cell death (PCD), while concentrations of 12.5 microg/ml induced a morphology of blister formation or blister cell death (BCD). To elucidate the possible role of Bcl-2 in this dual cell death modality induced by sanguinarine, K562 and the high Bcl-2-expressing JM1 cells were treated with sanguinarine concentrations of 1.5 microg/ml and 12.5 microg/ml respectively, and multiple parameters of their effects were studied using light and electron microscopy, terminal deoxynucleotidyl transferase (TdT) end-labeling, 51Cr release, trypan blue exclusion, propidium iodide exclusion, and annexin-V binding. In general, we found that, while K562 cells underwent PCD and BCD when treated with sanguinarine, JM1 cells failed to undergo either PCD or BCD under the same experimental conditions. Thus, the over-expression of anti-apoptotic Bcl-2 may have prevented sanguinarine from inducing PCD and BCD in JM1 cells. These results indicate that the resistance of JM1 cells to the alkaloid sanguinarine may have been due to an anti-BCD role played by Bcl-2, in addition to its widely reported anti-apoptotic role.
Weerasinghe
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P
Faculty of Medicine, Memorial University of Newfoundland, Canada. priyaw@mit.edu
Hallock
S
S
Tang
S C
SC
Liepins
A
A
D000470:Alkaloids / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D053119:Benzophenanthridines; D002470:Cell Survival / Q000187:drug effects; D002857:Chromium / Q000378:metabolism; D002860:Chromium Radioisotopes; D004249:DNA Damage / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D020287:In Situ Nick-End Labeling; D007546:Isoquinolines; D020014:K562 Cells / Q000187:drug effects* / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis / Q000378:metabolism*
D000470:Alkaloids; D000970:Antineoplastic Agents; D053119:Benzophenanthridines; D002860:Chromium Radioisotopes; D007546:Isoquinolines; D019253:Proto-Oncogene Proteins c-bcl-2; D002857:Chromium; C005705:sanguinarine