Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 1487-1495 |
| Number of pages | 9 |
| Journal | Biochemical Pharmacology |
| Volume | 61 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - 2001 Jun 15 |
| Externally published | Yes |
Bibliographical note
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.
Keywords
- 1α,25-Dihydroxyvitamin D
- Extracellular signal-regulated kinase
- HL-60 cell differentiation
- Protein kinase C
- Silibinin
ASJC Scopus subject areas
- Biochemistry
- Pharmacology