P. Pantazis et al., ALTERED SENSITIVITIES TO ANTICANCER AND DIFFERENTIATION AGENTS IN ETOPOSIDE-RESISTANT HUMAN MYELOID-LEUKEMIA U-937 CELLS, Journal of hematotherapy, 7(1), 1998, pp. 81-92
Citations number
52
Categorie Soggetti
Transplantation,Hematology,"Medicine, Research & Experimental
We previously have exposed U-937 human leukemia cells to stepwise incr
eased concentrations of the anticancer drug etoposide, and this treatm
ent has resulted in stable sublines (termed U-937/RE) exhibiting vario
us extents of resistance to the drug and constitutively expressing c-f
ms mRNA, a specific marker of monocytic differentiation. In this repor
t, we pursued studies to show that the P-glycoprotein blocker, verapam
il, partially restores sensitivity to etoposide in U-937/RE cells, Fur
ther, the U-937/RE cells exhibit differential sensitivities to compoun
ds that induce maturation of U-937 cells, as judged by the ability to
reduce nitroblue tetrazolium and by morphologic changes, and increased
sensitivities to apoptosis induction by the cytokines tumor necrosis
factor (TNF) and lymphotoxin (LT) and the anticancer drugs 9-nitrocamp
tothecin and doxorubicin. In addition, the U-937/RE cells, xenografted
in immunodeficient mice, demonstrate decreased or no ability to induc
e tumors. Taken together, these findings indicate that U-937/RE cells
differ from the parental U-937 cells in several functional properties
and can serve as models to develop protocols for treatment of human le
ukemia.