ABSTRACT
Matrine is a major component of Sophora Flavescens and has been reported to stimulate differentiation of erythroleukemia cells. Here we show that matrine inhibits cell proliferation or induces apoptosis in a cell type-specific manner. The latter effect was investigated in more detail in the p53 deficient erythroleukemia cell line, K562. Matrine exposure induced apoptosis in a time- and dose-dependent manner in these cells. Interestingly, co-treatment with etoposide potentiated apoptosis. Further analysis of matrine-induced apoptotic changes revealed that E2F-1 and Apaf-1 were upregulated, whereas Rb was downregulated after 24 h of exposure. This was followed by Bax translocation, cytochrome c release, and caspase-9 and -3 activation. These results demonstrate that matrine triggers apoptosis of K562 cells primarily through the mitochondrial pathway and that matrine is a potential anti-tumor drug.
Subject(s)
Alkaloids/pharmacology , Antineoplastic Agents, Phytogenic/pharmacology , Apoptosis/drug effects , E2F1 Transcription Factor/biosynthesis , Leukemia, Erythroblastic, Acute/physiopathology , Mitochondria/drug effects , Quinolizines/pharmacology , Apoptotic Protease-Activating Factor 1/biosynthesis , Caspase 3/metabolism , Caspase 9/metabolism , Cytochromes c/metabolism , Dose-Response Relationship, Drug , Down-Regulation/drug effects , Drug Synergism , Enzyme Activation/drug effects , Etoposide/pharmacology , HeLa Cells , Humans , K562 Cells , Leukemia, Erythroblastic, Acute/metabolism , Mitochondria/metabolism , Protein Transport/drug effects , Retinoblastoma Protein/metabolism , Time Factors , Tumor Suppressor Protein p53/deficiency , U937 Cells , Up-Regulation/drug effects , bcl-2-Associated X Protein/metabolism , MatrinesABSTRACT
Huangqi (Astragalus membranaceus), a traditional Chinese medicine, has been used to ameliorate side effects of cancer chemotherapy in China. However, little is known about its molecular mechanisms. Here we show that induction of K562 or HEL cells with 1.5 mg/ml of Huangqi (Hex) (Components extracted from Huangqi) for 3-5 d results in the expression of beta-globin gene in both cell lines and leads to terminal differentiation. Moreover, the apoptosis in HEL cells can be induced by increasing concentration of Huangqi (Hex) to 4.5 mg/ml for 3-5 d. Upregulation of Apaf-1, caspase-3 and acetylcholinesterase (AChE) in HEL cells may play a crucial role in the process of apoptosis. The prospect of inducing expression of adult (beta) globin gene and apoptosis selectively in cancer cells is obviously attractive from a therapeutic point of view.
Subject(s)
Apoptosis/drug effects , Cell Differentiation/drug effects , Drugs, Chinese Herbal/pharmacology , Globins/metabolism , Leukemia, Erythroblastic, Acute/pathology , Leukemia, Erythroblastic, Acute/physiopathology , Acetylcholinesterase/metabolism , Astragalus Plant , Astragalus propinquus , Caspase 3 , Caspases/metabolism , Cell Line, Tumor , Dose-Response Relationship, Drug , Enzyme Activation/drug effects , Gene Expression Regulation, Neoplastic , Humans , K562 CellsABSTRACT
A human erythroleukemia cell line(K562 cells)was used as a model to study the effect of interleukin-3(IL-3) on human globin gene expression in the cells. The results showed that the beta-globin gene was not expressed in uninduced K562 cells however, it was expressed when K562 cells were induced for 3 or 5 days by IL-3. The expression of alpha- and gamma-globin gene were not much different between IL-3 induced and uninduced K562 cells. Using the method of benzidine-dyeing, it was observed that the percentage of blue cells was significantly increased when K562 cells were induced by IL-3. It suggested that IL-3 could not only activate the exp-ression of beta-globin gene in K562 cells, but also induce the synthesis of hemoglobin. Therefore, IL-3 may play a critical role in inducing K562 cells to terminal differentiation.