Effect of the Anti‐Breast Cancer Drug Tamoxifen on Ca²⁺ Movement in Human Osteosarcoma Cells

Abstract

Abstract:The anti-breast cancer drug tamoxifen has recently been shown to cause an increase in [Ca 2π ] i in renal tubular cells, breast cells and bladder cells. Because tamoxifen is known to interact with oestrogens leading to modulation of bone metabolism, the present study was aimed at exploring whether tamoxifen could alter Ca 2π signaling in human osteoblastlike MG63 cells. Cytosolic free Ca 2π levels were recorded by using the Ca 2π -sensitive dye fura-2. Tamoxifen induced a sustained [Ca 2π ] i increase at concentrations above 1 mM with an EC 50 of 8 mM. Removal of extracellular Ca 2π reduced the response by 40%, suggesting that tamoxifen induced both Ca 2π influx and store Ca 2π release. Tamoxifen-induced Ca 2π influx was confirmed as tamoxifen caused Mn 2π influx-induced quench of fura-2 fluorescence. In Ca 2π -free medium, pretreatment with 10 mM tamoxifen abolished the [Ca 2π ] i increase induced by 1 mM thapsigargin (an endoplasmic reticulum Ca 2π pump inhibitor), and by 2 mM carbonylcyanide m-chlorophenylhydrazone (a mitochondrial uncoupler). Conversely, pretreatment with thapsigargin and carbonylcyanide m-chlorophenylhydrazone only reduced 64% of tamoxifeninduced [Ca 2π ] i increases. Addition of 2 mM U73122 to inhibit phospholipase C activity abolished the [Ca 2π

Tamoxifen Inhibits TRPV6 Activity via Estrogen Receptor–Independent Pathways in TRPV6-Expressing MCF-7 Breast Cancer Cells

“…Because, in nondepolarizing cells, the majority of the basal calcium influx occurs through SOCC, the possible effect of tamoxifen on native TRPV6 activity was masked. Tamoxifen also exerts the same effect on SOCC activity in several cell types such as human oral cancer cells, CHO-K1 cells, human osteosarcoma cells, and ZR-75-1 human breast cancer cells (34)(35)(36)(37). This effect was shown not to be mediated by ERs.…”

Capsazepine elevates intracellular Ca2+ in human osteosarcoma cells, questioning its selectivity as a vanilloid receptor antagonist

“…Human MG63 osteosarcoma cells have been shown to possess Ca 2+ stores in the endoplasmic reticulum, mitochondria and other unknown compartments (Kuo et al, 2003;Jan et al, 2002;Lu et al, 2002). Regarding the Ca 2+ stores of capsazepine-induced [Ca 2+ ] i rise, the thapsigargin-sensitive endoplasmic reticulum store appears to play a major role because capsazepine pretreatment depleted thapsigargin-sensitive Ca 2+ stores.…”

Effects of MK‐886, a leukotriene synthesis inhibitor, on [Ca2+]i and apoptosis in MG63 human osteosarcoma cells

“…In osteoblastic cells, Babich et al [1997] [Chang et al, 2005], 4,4 0 -dithiodipyridine [Kuo et al, 2003], CP55,940 [Lu et al, 2002b], and tamoxifen [Lu et al, 2002a]. Additionally, it appears that phospholipase C-dependent pathways did not play a role in MK-886-induced Ca MK-886 is cytotoxic in several cell types including Jurkat T lymphocytes [Deshpande and Kehrer., 2006], HT-29 cells [Kleban et al, 2006], HL-60 cells [Stika et al, 2006], gastric cancer cells [Fan et al, 2004], and rat arterial myocytes [Smirnov et al, 1998].…”