TY - JOUR
T1 - Induction of human promyelocytic leukemia HL-60 cell differentiation into monocytes by silibinin
T2 - Involvement of protein kinase C
AU - Kang, So N.
AU - Lee, Mi H.
AU - Kim, Kyeong Man
AU - Cho, Daeho
AU - Kim, Tae S.
N1 - Funding Information:
We would like to thank Drs. J.W. Lee, H.J. Han, and J.H. Cheong (all with Chonnam National University, Korea) for providing valuable reagents and instruments. This work was supported by grants from the Korea Science and Engineering Foundation (HRC 1998G0021) and in part from the GenoCheck Co., Ltd (Ansan, Korea) (GC 20001).
Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.
PY - 2001/6/15
Y1 - 2001/6/15
N2 - The effect of silibinin, an active component of Silybum marianum, on cellular differentiation was investigated in the human promyelocytic leukemia HL-60 cell culture system. Treatment of HL-60 cells with silibinin inhibited cellular proliferation and induced cellular differentiation in a dose-dependent manner. Cytofluorometric analysis and morphologic studies indicated that silibinin induced differentiation of HL-60 cells predominantly into monocytes. Importantly, strongly synergistic induction of differentiation into monocytes was observed when silibinin was combined with 5 nM 1α,25-dihydroxyvitamin D3 [1,25-(OH)2D3], a well-known differentiation inducer of HL-60 cells into the monocytic lineage. Silibinin enhanced protein kinase C (PKC) activity and increased protein levels of both PKCα and PKCβ in 1,25-(OH)2D3-treated HL-60 cells. PKC and extracellular signal-regulated kinase (ERK) inhibitors significantly inhibited HL-60 cell differentiation induced by silibinin alone or in combination with 1,25-(OH)2D3, indicating that PKC and ERK may be involved in silibinin-induced HL-60 cell differentiation.
AB - The effect of silibinin, an active component of Silybum marianum, on cellular differentiation was investigated in the human promyelocytic leukemia HL-60 cell culture system. Treatment of HL-60 cells with silibinin inhibited cellular proliferation and induced cellular differentiation in a dose-dependent manner. Cytofluorometric analysis and morphologic studies indicated that silibinin induced differentiation of HL-60 cells predominantly into monocytes. Importantly, strongly synergistic induction of differentiation into monocytes was observed when silibinin was combined with 5 nM 1α,25-dihydroxyvitamin D3 [1,25-(OH)2D3], a well-known differentiation inducer of HL-60 cells into the monocytic lineage. Silibinin enhanced protein kinase C (PKC) activity and increased protein levels of both PKCα and PKCβ in 1,25-(OH)2D3-treated HL-60 cells. PKC and extracellular signal-regulated kinase (ERK) inhibitors significantly inhibited HL-60 cell differentiation induced by silibinin alone or in combination with 1,25-(OH)2D3, indicating that PKC and ERK may be involved in silibinin-induced HL-60 cell differentiation.
KW - 1α,25-Dihydroxyvitamin D
KW - Extracellular signal-regulated kinase
KW - HL-60 cell differentiation
KW - Protein kinase C
KW - Silibinin
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U2 - 10.1016/S0006-2952(01)00626-8
DO - 10.1016/S0006-2952(01)00626-8
M3 - Article
C2 - 11377378
AN - SCOPUS:0035877237
SN - 0006-2952
VL - 61
SP - 1487
EP - 1495
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
IS - 12
ER -