Effect of sertraline on [Ca2+]i and viability of human MG63 osteosarcoma cells. (April 2013)

• Record Type: Journal Article
• Authors: Lin, Ko-Long; Chi, Chao-Chuan; Lu, Ti; Tseng, Li-Ling; Wang, Jue-Long; Lu, Yi-Chau; Jan, Chung-Ren
• Is Part Of: Drug and chemical toxicology. Volume 36:Number 2(2013:Apr.)
• Page Start: 231
• Page End: 240
• Publication Date: 2013-04
• Subjects: Toxicology -- Periodicals; Drugs -- Toxicology -- Periodicals; Toxicology, Experimental -- Periodicals; 615.9005
• DOI: 10.3109/01480545.2012.710625
• Languages: English
• ISSNs: 0148-0545

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <p>The antidepressant, sertraline, has been shown to have diverse <italic>in vitro</italic> effects. This study examined whether sertraline altered [Ca<sup>2+</sup>]<sub>i</sub> in MG63 human osteosarcoma cells by using fura-2 as a Ca<sup>2+</sup>-sensitive fluorescent dye. At 50–200 µM, sertraline induced a [Ca<sup>2+</sup>]<sub>i</sub> rise in a concentration-dependent manner. Ca<sup>2+</sup> response was decreased by removing extracellular Ca<sup>2+</sup>, suggesting that Ca<sup>2+</sup> entry and release contributed to the [Ca<sup>2+</sup>]<sub>i</sub> signal. Sertraline-induced Ca<sup>2+</sup> entry was inhibited by nifedipine, La<sup>3+</sup>, Gd<sup>3+</sup>, and SK&F96365. When extracellular Ca<sup>2+</sup> was removed, pretreatment with the endoplasmic reticulum (ER) Ca<sup>2+</sup> pump inhibitor, thapsigargin, or 2, 5-di-tert-butylhydroquinone (BHQ) abolished the sertraline-evoked [Ca<sup>2+</sup>]<sub>i</sub> rise. Incubation with sertraline also abolished the thapsigargin or BHQ-induced [Ca<sup>2+</sup>]<sub>i</sub> rise. Inhibition of phospholipase C (PLC) with U73122 abolished the sertraline-induced [Ca<sup>2+</sup>]<sub>i</sub> rise. At 20–30 µM, overnight treatment with sertraline killed cells in a concentration-dependent manner. The cytotoxic effect of sertraline was not reversed by chelating cytosolic Ca<sup>2+</sup> with 1, 2-bis(2-aminophenoxy)ethane-N, N, N', N'-tetraacetic acid (BAPTA). Annexin V/propidium iodide staining data demonstrate that sertraline (30 µM) evoked apoptosis. Sertraline (20 and 30 µM) also increased levels of reactive oxygen species. Together, in human osteosarcoma cells, sertraline evoked a [Ca<sup>2+</sup>]<sub>i</sub> rise by inducing PLC-dependent Ca<sup>2+</sup> release from the ER and Ca<sup>2+</sup> entry by L-type Ca<sup>2+</sup> channels and store-operated Ca<sup>2+</sup> channels. Sertraline induced cell death that may involve apoptosis by mitochondrial pathways.</p> </abstract>