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題名 | Effect of Antidepressant Doxepin on Ca²⁺ Homeostasis and Viability in PC3 Human Prostate Cancer Cells= |
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作者 | Lu, Ti; Chou, Chiang-ting; Liang, Wei-zhe; Yu, Chia-cheng; Chang, Hong-tai; Kuo, Chun-chi; Chen, Wei-chuan; Kuo, Daih-huang; Ho, Chin-man; Shieh, Pochuen; Jan, Chung-ren; |
期刊 | The Chinese Journal of Physiology |
出版日期 | 20150600 |
卷期 | 58:3 2015.06[民104.06] |
頁次 | 頁178-187 |
分類號 | 418.214 |
語文 | eng |
關鍵詞 | Ca²⁺; Doxepin; Endoplasmic reticulum; Human prostate cancer cells; Phospholipase C; Protein kinase C; |
英文摘要 | The effect of the antidepressant doxepin on cytosolic Ca2+ concentrations ([Ca2+]i ) and viability in PC3 human prostate cancer cells was explored. The Ca2+-sensitive fluorescent dye fura-2 was applied to measure [Ca2+]i . Doxepin at concentrations of 500-1000 µM induced a [Ca2+]i rise in a concentrationdependent manner. The response was reduced partly by removing Ca2+. Doxepin-evoked Ca2+ entry was suppressed by Ca2+ entry blockers (nifedipine, econazole, SK&F96365), and protein kinase C (PKC) modulators. In the absence of extracellular Ca2+, incubation with the endoplasmic reticulum Ca2+ pump inhibitor thapsigargin or 2,5-di-tert-butylhydroquinone (BHQ) partly inhibit doxepin-induced [Ca2+]i rise. Incubation with doxepin nearly inhibited thapsigargin or BHQ-induced [Ca2+]i rise. Inhibition of phospholipase C (PLC) with U73122 failed to alter doxepin-induced [Ca2+]i rise. At concentrations of 200-250 µM, doxepin killed cells in a concentration-dependent manner. This cytotoxic effect was not reversed by chelating cytosolic Ca2+ with 1,2-bis(2-aminophenoxy)ethane-N,N,N’,N’- tetraacetic acid/acetoxy methyl (BAPTA/AM). Annexin V/PI staining data implied that doxepin (200 and 250 µM) did not induce apoptosis. Collectively, in PC3 cells, doxepin induced a [Ca2+]i rise by evoking PLC-independent Ca2+ release from stores including the endoplasmic reticulum and Ca2+ entry via PKC-sensitive store-operated Ca2+ channels. Doxepin caused cell death that was independent of [Ca2+]i rises. |
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