Tamoxifen-induced enhancement of calcium signaling in glioma and MCF-7 breast cancer cells

The antiestrogen tamoxifen is commonly used to treat breast cancer, but it also has therapeutic activity in several other types of cancer. Many of the se tumors, including malignant gliomas, are estrogen receptor negative. Non etheless, high concentrations of tamoxifen can directly reduce cell prolife ration in some of these tumors and induce apoptosis, In this study, the rol e of tamoxifen in calcium signaling and calcium-induced cell death was stud ied in both malignant glioma cell lines and MCF-7 breast cancer cells. Tamo xifen potently increased the spatial expansion of calcium waves by 30-150% while significantly enhancing and prolonging agonist-induced calcium elevat ions. Furthermore, tamoxifen pretreatment accelerated calcium ionophore-ind uced death by more than 20 min, suggesting that tamoxifen lowered cellular resistance to calcium loads. In contrast to its potentiating of calcium sig naling in tumors, tamoxifen had no significant effect on calcium signaling in cultures of primary astrocytes from either human or rat brain. This stud y demonstrates the existence of calcium signaling in breast cancer and glio ma cells and identifies tamoxifen as a potential modulator of tumor-associa ted calcium signaling.