ABSTRACT
The effects of midazolam (MID) on the in vitro growth and differentiation of two murine myeloid leukemia WEHI 3B (JCS) and M1 cells were studied. MID inhibits the proliferation of both M1 and JCS cells in a dose-dependent manner. At the concentration of 10 micrograms/ml, MID was found to induce both monocytic and granulocytic differentiation of the JCS but not M1 cells. Induction of morphological differentiation of the JCS cells was also associated with the enhanced expression of the differentiation antigens Mac-1, F4/80, and Gr-1 for the cells. Results from mRNA phenotyping experiments also indicated that the expression of tumor necrosis factor (TNF-alpha) and neutrophil-specific J11d differentiation marker was significantly upregulated in MID-treated JCS cells. In addition, the phagocytic activity of MID-treated JCS cells was increased towards opsonized yeast cells. Results from this investigation suggested that MID may be used as an inducer for further study on the mechanisms of differentiation in these myeloid leukemia cells.
Subject(s)
Anesthetics, Intravenous/pharmacology , Leukemia, Myeloid/drug therapy , Midazolam/pharmacology , Animals , Cell Differentiation/drug effects , Cell Division/drug effects , Drug Evaluation, Preclinical , Flow Cytometry , Leukemia, Myeloid/pathology , Mice , Phagocytosis/drug effects , Phenotype , RNA, Messenger/geneticsABSTRACT
The effects of biochanin A on the growth and differentiation of a recently characterized myeloid leukemia cell line WEHI-3B (JCS) were investigated. Biochanin A not only inhibited the growth of JCS cells in a dose-dependent manner (0 - 200 microM) but also induced the morphological differentiation of JCS cells. The phagocytic activity of biochanin A-treated JCS cells was also increased. Flow cytometric analysis showed that the expression of macrophage differentiation markers Mac-1 and F4/80 was up-regulated in biochanin A-treated JCS cells. The expression level of Mac-1 was higher than that of F4/80. The expression of cytokine genes was studied by reverse transcription-polymerase chain reaction (RT-PCR) and cycle titration. mRNA levels of IL-1alpha, IL-1beta and IL-4 were found to be up-regulated at 46 hours after incubation of JCS cells with biochanin A. Although the expression of LIF was also up-regulated, the LIF receptor gene was not expressed in the uninduced or induced JCS cells. Our results suggest that IL-1alpha, IL-1beta and IL-4 may act on the later stage of biochanin A-mediated differentiation of JCS cells.
