We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
The Mechanism of Sertraline-induced [Ca<sup>2+</sup>]<sub>i</sub> Rise in Human PC3 Prostate Cancer Cells.
- Authors
Huang, Jong-Khing; Chang, Hong-Tai; Chou, Chiang-Ting; Shu, Su-Shung; Kuo, Chun-Chi; Tsai, Jeng-Yu; Liao, Wei-Chuan; Wang, Jue-Long; Lin, Ko-Long; Lu, Yi-Chau; Chen, I-Shu; Liu, Shuih-Inn; Ho, Chin-Man; Jan, Chung-Ren
- Abstract
The effect of sertraline, an antidepressant, on cytosolic-free Ca2+ levels ([Ca2+]i) in human cancer cells is unclear. This study examined whether sertraline altered basal [Ca2+]i levels in suspended PC3 human prostate cancer cells by using fura-2 as a Ca2+-sensitive fluorescent probe. At concentrations of 10-150 lM, sertraline induced a [Ca2+]i rise in a concentration- dependent fashion. The Ca2+signal was reduced partly by removing extracellular Ca2+indicating that Ca2+entry and release both contributed to the [Ca2+]i rise. Sertraline induced Mn2+ influx, leading to quench of fura-2 fluorescence suggesting Ca2+ influx. This Ca2+ influx was inhibited by the suppression of store-operated Ca2+ channels or by the modulation of protein kinase C activity. In Ca2+-free medium, pre-treatment with the endoplasmic reticulum Ca2+ pump inhibitor thapsigargin or 2,5-di-(t-butyl)-1,4-hydroquinone nearly abolished sertraline-induced Ca2+release. Conversely, pre-treatment with sertraline greatly reduced the inhibitor-induced [Ca2+]i rise, suggesting that sertraline released Ca2+from the endoplasmic reticulum. Inhibition of phospholipase C inhibited sertraline-induced [Ca2+]i rise. At 20-30 μM, sertraline killed cells in a concentrationdependent manner. The cytotoxic effect of sertraline was enhanced by chelating cytosolic Ca2+ with 1,2-bis(2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid /AM. Annexin V-FITC data suggest that sertraline (20 and 30 μM) evoked apoptosis in a concentration-dependent manner. Together, in PC3 human prostate cancer cells, sertraline induced [Ca2+]i rises by causing phospholipase C-dependent Ca2+ release from the endoplasmic reticulum and via multiple Ca2+ influx pathways that involve store-operated Ca2+ channels. Sertraline also induced apoptosis that was not triggered by [Ca2+]i rise.
- Subjects
SERTRALINE; PROSTATE cancer; CANCER cells; FLUORESCENT probes; PROTEIN kinases; ENDOPLASMIC reticulum
- Publication
Basic & Clinical Pharmacology & Toxicology, 2011, Vol 109, Issue 2, p103
- ISSN
1742-7835
- Publication type
Article
- DOI
10.1111/j.1742-7843.2011.00690.x