Calcium channel antagonist properties of the antineoplastic antiestrogen tamoxifen in the PC12 neurosecretory cell line.

In view of existing evidence that Ca2+ may be important for tumor cell growth and metastasis, we investigated the effects of three antineoplastic drugs on K+-stimulated 45Ca2+ uptake through voltage-dependent Ca2+ channels of the PC12 neurosecretory cell line. The agents chosen for study (vinblastine, doxorubicin, and tamoxifen) were those previously shown to inhibit Ca2+/calmodulin- or Ca2+/phospholipid-activated protein kinases. Neither vinblastine nor doxorubicin altered 45Ca2+ uptake at concentrations that inhibit these Ca2+-dependent enzymes. However, tamoxifen reduced uptake [50% inhibitory dose, 8.6 +/- 0.9 (SE) microM] and competed for Ca2+ channel antagonist binding sites labeled by [3H]-(+)PN200-110 (ki = 2.2 +/- 0.3 microM). Ca2+ channel antagonist properties may contribute to the effects of antineoplastic agents such as tamoxifen.