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Effect of tamoxifen on cell lines displaying the multidrug-resistant
phenotype [see comments]
E Berman, M Adams, R Duigou-Osterndorf, L Godfrey, B Clarkson and M Andreeff
Laboratory of Hematopoietic Cell Kinetics, Memorial Sloan-Kettering Cancer
Center, New York, NY 10021.
We examined the effect of tamoxifen (Tmx), verapamil, and daunorubicin
(DNR) in two cell lines that displayed the multidrug-resistant (MDR)
phenotype and used laser flow cytometry to quantitate intracellular DNR
content. In the vinblastine-resistant human lymphoblastic lymphoma cell
line CEM-VBL, simultaneous incubation of DNR with Tmx 10 mumol/L or Tmx 50
mumol/L increased intracellular DNR fluorescence in a dose-dependent manner
and demonstrated an uptake pattern similar to that seen with DNR and
verapamil. Similar results were obtained in the vincristine- resistant
human myeloid leukemia cell line HL-60/RV+. Cellular retention of DNR was
also measured in both cell lines and results suggested that continuous
exposure of the cells to Tmx resulted in higher intracellular DNR content
compared with cells resuspended in fresh medium. No effect of Tmx or
verapamil was observed in the drug- sensitive parent cell lines CEM or
HL-60. Clonogenic experiments were then performed to determine whether Tmx
was itself inhibitory to cell growth or whether Tmx potentiated DNR
cytotoxicity. Tmx 10 mumol/L did not significantly inhibit either CEM-VBL
or HL-60/RV+ cells after a 3- hour exposure followed by culture in
methylcellulose. Tmx 50 mumol/L was significantly more inhibitory in both
cell lines. However, cells that had been incubated with DNR and Tmx 10
mumol/L demonstrated a marked increment in growth inhibition compared with
cells that had been incubated with DNR alone or Tmx 10 mumol/L alone. Based
on the data presented here, we suggest that clinical testing of Tmx and DNR
be pursued in the setting where MDR may play a role.
Volume 77,
Issue 4,
pp. 818-825,
02/15/1991
Copyright © 1991 by The American Society of Hematology
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