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Cancer letters

Bepridil enhances in vitro antitumor activity of antiestrogens in human brain tumor cells.


PMID 9018108

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.

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