In vitro inhibitory effects of imatinib mesylate on stromal cells and hematopoietic progenitors from bone marrow

Abstract

Imatinib mesylate (IM) is used to treat chronic myeloid leukemia (CML) because it selectively inhibits tyrosine kinase, which is a hallmark of CML oncogenesis. Recent studies have shown that IM inhibits the growth of several non-malignant hematopoietic and fibroblast cells from bone marrow (BM). The aim of the present study was to evaluate the effects of IM on stromal and hematopoietic progenitor cells, specifically in the colony-forming units of granulocyte/macrophage (CFU-GM), using BM cultures from 108 1.5- to 2-month-old healthy Swiss mice. The results showed that low concentrations of IM (1.25 µM) reduced the growth of CFU-GM in clonogenic assays. In culture assays with stromal cells, fibroblast proliferation and α-SMA expression by immunocytochemistry analysis were also reduced in a concentration-dependent manner, with a survival rate of approximately 50% with a dose of 2.5 µM. Cell viability and morphology were analyzed using MTT and staining with acrydine orange/ethidium bromide. Most cells were found to be viable after treatment with 5 µM IM, although there was gradual growth inhibition of fibroblastic cells while the number of round cells (macrophage-like cells) increased. At higher concentrations (15 µM), the majority of cells were apoptotic and cell growth ceased completely. Oil red staining revealed the presence of adipocytes only in untreated cells (control). Cell cycle analysis of stromal cells by flow cytometry showed a blockade at the G0/G1 phases in groups treated with 5-15 µM. These results suggest that IM differentially inhibits the survival of different types of BM cells since toxic effects were achieved.

In Situ Mannosylated Nanotrinity-Mediated Macrophage Remodeling Combats Candida albicans Infection

“…BMDMs were more sensitive to imatinib than J774A.1 macrophages when the drug concentration reached to 25 μM. When the concentration of imatinib was lower than 5 μM, no significant toxicity was observed in both J774A.1 macrophages and BMDMs, which was consistent with previous report . All of the above results indicated that MC-NPs-IM, C-NPs-IM, and NPs-IM have good biocompatibility.…”

“…When the concentration of imatinib was lower than 5 μM, no significant toxicity was observed in both J774A.1 macrophages and BMDMs, which was consistent with previous report. 22 All of the above results indicated that MC-NPs-IM, C-NPs-IM, and NPs-IM have good biocompatibility. According to the results of the cytotoxicity test, the drug concentration used in the subsequent experiment was 5 μM.…”