[Effects of arsenic trioxide on K562 cells stably expressing two promyelocytic leukemia-specific fusion proteins].
OBJECTIVE
To illustrate the possible roles of acute promyelocytic leukemia-specific chimeric proteins PML-RARalpha and PLZF-RARalpha in the effects of arsenic trioxide (As(2)O(3)).


METHODS
K562 sublines stably expressing PML-RARalpha (K(PML() and PLZF-RARalpha (K(PLZF)) were established by retrovirus transfection with K(V) transfected empty vectors as controls. Effects of As(2)O(3) and all-trans retinoic acid (ATRA) on these sublines were analyzed through cell count, morphology, measurement of cellular DNA contents and differentiation antigens on flow cytometry. Subcellular distributions of PML-RARalpha proteins were observed with immunofluorescence.


RESULTS
1.0 micromol/L of As(2)O(3) did not induce cell apoptosis and differentiation, but it significantly inhibited the growth of K(V) sublines. As(2)O(3) showed the similar but more potent effects in K(PML) and K(PLZF) sublines. 1.0 micromol/L As(2)O(3) treatment for 3 days induced growth inhibition by 32% +/- 3%, 57% +/- 4% and 54% +/- 6%, respectively in K(V), K(PML) and K(PLZF) sublines. 1.0 micromol/L ATRA also exerted, to a less extent than As(2)O(3), growth-inhibitory effects in K(V) sublines, which became more obvious in K(PML) but not in K(PLZF) sublines. In addition, PML/PML-RARalpha proteins were decreased and even disappeared in K(V) and K(PML) sublines with the treatment of 1.0 micromol/L As(2)O(3) for 48 hours.


CONCLUSIONS
PML-RARalpha and PLZF-RARalpha markedly enhance growth-inhibitory effects of As2)O3) on K562 cells.
Zhou
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L
Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Second Medical University, Shanghai 200025, China.
Chen
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G
Pan
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L
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D015870:Gene Expression; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D020014:K562 Cells; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism*; D010087:Oxides / Q000494:pharmacology*; D014212:Tretinoin / Q000494:pharmacology
D000970:Antineoplastic Agents; D001152:Arsenicals; D006131:Growth Inhibitors; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; D010087:Oxides; C118318:PLZF-RARalpha fusion protein, human; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein; D014212:Tretinoin; D000077237:Arsenic Trioxide