Potentiation of tamoxifen activity by verapamil in a human breast cancer cell line.
The tumor cell growth inhibitory activity of tamoxifen was enhanced significantly by verapamil treatment in an estrogen receptor positive human breast cancer cell line, MCF-7. Treatment of MCF-7 cells with 5 and 10 micrograms/mL verapamil produced a 1.8- and 2.8-fold increase, respectively, in tamoxifen activity. Unlike reversal of multi-drug resistance, the verapamil-mediated increase in tamoxifen activity was not associated with enhanced drug accumulation. Tamoxifen treatment alone or in combination with verapamil did not affect the activity of protein kinase C, an enzyme implicated in the anti-tumor activity of tamoxifen. Addition of 17 beta-estradiol in the cell survival assay system partially abrogated the modulatory effect of verapamil. These data suggest that potentiation of tamoxifen activity by verapamil may involve interaction of this agent with the estrogen receptor. In conclusion, potentiation of tamoxifen activity by calcium channel blockers represents a novel approach for improving the therapeutic results with tamoxifen in women with breast cancer.
Gupta
V
V
Cancer Research Laboratory, Mercy Cancer Center, Mercy Hospital, Pittsburgh, PA 15219.
Kamath
N
N
Tkalcevic
G T
GT
Singh
S V
SV
D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004357:Drug Synergism; D005260:Female; D006801:Humans; D011493:Protein Kinase C / Q000032:analysis; D011960:Receptors, Estrogen / Q000187:drug effects; D013629:Tamoxifen / Q000378:metabolism / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014700:Verapamil / Q000494:pharmacology*
D011960:Receptors, Estrogen; D013629:Tamoxifen; D014700:Verapamil; D011493:Protein Kinase C