Dihydroartemisinin down-regulates the expression of transferrin receptor in myeloid leukemia cells.
- Author:
Zeng WANG
1
;
Hui-Jun ZHOU
Author Information
1. College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
- Publication Type:Journal Article
- MeSH:
Antineoplastic Agents, Phytogenic;
administration & dosage;
pharmacology;
Artemisinins;
administration & dosage;
pharmacology;
Cell Proliferation;
drug effects;
Dose-Response Relationship, Drug;
Down-Regulation;
HL-60 Cells;
Humans;
K562 Cells;
RNA, Messenger;
metabolism;
Receptors, Transferrin;
genetics;
metabolism;
Transferrin;
metabolism
- From:
Acta Pharmaceutica Sinica
2008;43(6):576-583
- CountryChina
- Language:Chinese
-
Abstract:
This article reports the effect of dihydroartemisinin (DHA) on transferrin receptor (TfR) in myeloid leukemia cells by establishing the model of normal iron HL60 and K562 cells and iron overload K562 cells in vitro. The TfR content of myeloid leukemia cells was determined by flow cytometry, and the effect of DHA on iron content in K562 cells was determined by atomic absorption spectrophotometric analysis. Furthermore, the inhibitory effect of DHA on the anti-proliferation and expression of TfR protein and mRNA in myeloid leukemia cells was studied. As a result, DHA effectively decreased the TfR content and down-regulated TfR protein expression in normal iron HL60 and K562 cells in a dose- and time-dependent manner and inhibited the cell proliferation. The IC50 were 1.74 and 11.33 micromol x L(-1), respectively. DHA exerted more pronounced inhibitory action on expression of TfR protein and mRNA in iron overload K562 cells. Compared to normal iron K562 cells, the TfR protein and mRNA levels were lowered by 28.1% (P < 0.01) and 26. 2% (P < 0. 05) , respectively, after DHA treatment for 48 h in iron overload K562 cells. Moreover, DHA decreased the iron content of iron overload K562 cells and inhibited the proliferation of iron overload K562 cells more potently. DHA effectively down-regulated the TfR content as well as expression of TfR protein and mRNA in normal iron myeloid leukemia cells. DHA also inhibited the proliferation of HL60 and K562 cells. The anti-proliferation effect of DHA on iron overload K562 cells was more striking.