Abstract：
:verapamil, a calcium-influx blocker, enhanced the cytotoxicity of vincristine (VCR) in vitro 6- to 12-fold in eight human hemopoietic tumor cell lines established from acute lymphatic leukemia, acute myelogenous leukemia, and Burkitt's lymphoma. Great enhancement of VCR cytotoxicity was obtained in a VCR-resistant subline of K562 myelogenous leukemia. A maximum of approximate 100-fold increase in VCR cytotoxicity occurred. Heterogeneity in VCR sensitivity (80-fold difference in sensitivity) was observed in vitro among these human tumor cells. BALL and Daudi cells of B-cell type were more susceptible to VCR. At 6.6 or 20 microM of verapamil, the values for the concentration of drug required for 50% inhibition of cell growth for each cell line fell into a rather narrow range, and heterogeneity in VCR sensitivity among cell lines was circumvented in vitro. Verapamil also enhanced the cytotoxicity of Adriamycin, although the extent of enhancement was considerably small. Enhancement of VCR cytotoxicity also occurred with other calcium antagonists and calmodulin inhibitors. At maximum effective concentration of these reagents, a 3- to 5-fold increase in VCR cytotoxicity occurred in K562 cells. In VCR-resistant K562 cells, a more prominent enhancement (20- to 45-fold) was observed with these reagents. VCR resistance was circumvented in vitro. The mechanism of enhancement of VCR cytotoxicity was explained by the enhanced accumulation of VCR in K562, especially in resistant cells.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Tsuruo T,Iida H,Tsukagoshi S,Sakurai Ysubject
Has Abstractpub_date
1983-05-01 00:00:00pages
2267-72issue
5eissn
0008-5472issn
1538-7445journal_volume
43pub_type
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