Phenylacetic acid halides inhibit estrogen receptor (ER)-positive MCF-7 cells, but not ER-negative human breast cancer cells or normal breast epithelial cells.
Phenylacetic acid (PA) derivatives and conjugates have been reported to have antiproliferative and antitumor properties against various types of cancers. Based on these findings, recent in vitro experiments were devised to examine the antiproliferative properties of a series of para substituted (Br, Cl, F, H, NO2 and OCH3) PAs. The in vitro screening protocal involved the plating of MCF-7 cells in a 96-well plate assay. After 1 day, the cells were exposed to the PA derivatives for 2 days (log phase of MCF-7 growth curve). Cells growth was determined by the Alamar blue dye reagent. The optical density data was analyzed and IC50 concentration values determined. The results showed that PA halide derivatives caused a significant decrease in proliferation of the MCF-7 cells. The order of antiproliferative activity was BR > Cl > or = F, with IC50 values (nM) of 10 +/- 0.005, 100 +/- 0.02 and 100 +/- 0.04, respectively. The OCH3, H and NO2 compounds showed no significant antiproliferative activity. PA halide derivatives may have similar actions as tamoxifen because they show specificity for estrogen receptor-positive cells.
Johnson
D E
DE
Department of Pharmacology, Meharry Medical College, Nashville, TN 37208, USA.
Ochieng
J
J
Evans
S L
SL
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D006801:Humans; D010648:Phenylacetates / Q000494:pharmacology*; D011960:Receptors, Estrogen / Q000032:analysis*; D013629:Tamoxifen / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D000964:Antimetabolites, Antineoplastic; D010648:Phenylacetates; D011960:Receptors, Estrogen; D013629:Tamoxifen; D004958:Estradiol