New calmodulin antagonists inhibit in vitro growth of human breast cancer cell lines independent of their estrogen receptor status

Calmodulin plays a key role in the regulation of cell proliferation and cal modulin antagonists may offer a new therapeutic approach in the treatment o f breast cancer. Three new specific calmodulin antagonists with improved po tency were synthesized and screened on human breast cancer cell lines known to be estrogen receptor (ER)-positive or -negative. These calmodulin antag onists significantly inhibited cell growth as measured by the MTT prolifera tion assay (p < 0.001). Their IC50 values were in the low micromolar range against both ER-positive and -negative variants of the MCF-7 cell line. Two other breast cancer cell lines (ER-positive T-47D and ER-negative MDA-MB-2 31) were also inhibited by these calmodulin antagonists with IC50 values in a similar range. The level of inhibition was independent of any stimulatio n of cell growth by estradiol. Calmodulin antagonists effectively reduced c ell growth of both ER-positive and -negative human breast cancer cell lines in vitro. Calmodulin antagonists represent a novel therapeutic approach re quiring further investigation. [(C) 2000 Lippincott Williams & Wilkins.].