title: Bepridil enhances in vitro antitumor activity of antiestrogens in human brain tumor cells.
abstract: The possible interaction between antiestrogens (tamoxifen, clomiphene and nafoxidine) and bepridil, a known Na+-Ca2+ exchange blocker, in the regulation of cell growth was investigated using U-373 MG human astrocytoma and SK-N-MC human neuroblastoma cells as model cellular systems. The co-treatment of bepridil with antiestrogens significantly enhanced the antiestrogen-induced inhibition of the tumor cell growth. This bepridil-induced enhanced growth inhibition was significantly blocked by the addition of BAPTA/AM, an intracellular Ca2+ chelator, implying that increased free intracellular Ca2+ concentration may be involved in these actions. Other Na+-Ca2+ exchange blockers such as nickel and benzamil, also significantly potentiated the antiestrogen-induced inhibition of the tumor cell growth. Taken together, the blockade of Na+-Ca2+ exchange mechanism by these drugs may cause prolongation of increased intracellular Ca2+ concentration, in turn leading to these potentiated growth inhibitions of the tumor cells. These results suggest that the combined treatment with bepridil and antiestrogens may be a potential strategy for chemotherapy of brain tumors.
authors.affiliation: Department of Physiology, College of Medicine, Kwandong University, Kangreung, South Korea.
authors.forename: Y S
authors.initials: YS
authors.lastname: Lee
authors.forename: R D
authors.initials: RD
authors.lastname: Wurster
mesh_terms: D015764:Bepridil / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000473:pathology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002996:Clomiphene / Q000494:pharmacology; D004357:Drug Synergism; D004965:Estrogen Antagonists / Q000494:pharmacology*; D006801:Humans; D009256:Nafoxidine / Q000494:pharmacology; D013629:Tamoxifen / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014410:Tumor Stem Cell Assay
chemical_list: D002121:Calcium Channel Blockers; D004965:Estrogen Antagonists; D013629:Tamoxifen; D002996:Clomiphene; D009256:Nafoxidine; D015764:Bepridil