Induction of human promyelocytic leukemia HL-60 cell differentiation into monocytes by arsenic sulphide: involvement of serine/threonine protein phosphatases.
The clinical efficacy of arsenic sulfide (As(4)S(4)), also known as realgar, in the treatment of leukemia in China is prompting people to explore the underlying mechanism. We examined the realgar-induced differentiation in human promyelocytic leukemia cell line HL-60. Cells exhibited proliferation inhibition when treated with 0.10-1.5 microM of realgar, and underwent monocytic differentiation as indicated by morphological changes, NBT reduction assay, and cytofluorometric analyses of the cell surface antigens, CD11b and CD14. Accompanying the differentiation, the activity of serine/threonine protein phosphatase type 1 (PP1) and type 2A (PP2A) were enhanced, whereas the activity of PP2B remained virtually the same compared to the control. When cells were treated with realgar in the presence of an inhibitor of PP1 and 2A or an inhibitor of PP2B, the differentiation of the cells was partially suppressed as revealed by NBT reduction assay and the expression of CD14. Our data demonstrate that realgar induces monocytic differentiation in HL-60 cells and that some serine/threonine protein phosphatases may be involved in the process.
Luo
Li-Yun
LY
Department of Chemical Biology, Peking University School of Pharmaceutical Sciences, 38 Xue Yuan Road, Beijing 100083, PR China.
Huang
Jian
J
Gou
Bao-Di
BD
Zhang
Tian-Lan
TL
Wang
Kui
K
D001152:Arsenicals / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D018922:HL-60 Cells; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy*; D009000:Monocytes / Q000166:cytology / Q000187:drug effects*; D010749:Phosphoprotein Phosphatases / Q000187:drug effects / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D013329:Structure-Activity Relationship; D013440:Sulfides / Q000494:pharmacology*; D013912:Threonine / Q000378:metabolism
D001152:Arsenicals; D013440:Sulfides; D013912:Threonine; C045816:arsenic trisulfide; D012694:Serine; D010749:Phosphoprotein Phosphatases