Induction of human promyelocytic leukemia HL-60 cell differentiation into monocytes by silibinin: involvement of protein kinase C.
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 1alpha,25-dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)], 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 PKCalpha and PKCbeta in 1,25-(OH)(2)D(3)-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)(2)D(3), indicating that PKC and ERK may be involved in silibinin-induced HL-60 cell differentiation.
Kang
S N
SN
College of Pharmacy, Chonnam National University, Kwangju 500-757, Republic of Korea.
Lee
M H
MH
Kim
K M
KM
Cho
D
D
Kim
T S
TS
D000975:Antioxidants / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009000:Monocytes / Q000502:physiology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D012838:Silymarin / Q000494:pharmacology*; D013250:Steroid Hydroxylases / Q000494:pharmacology
D000975:Antioxidants; D004791:Enzyme Inhibitors; D012838:Silymarin; D013250:Steroid Hydroxylases; C406322:vitamin D 1-alpha hydroxylase; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases