Effect of protriptyline on [Ca2+]i and viability in MG63 human osteosarcoma cells

IF 2.8 4区医学 Q2 TOXICOLOGY

Toxicology Mechanisms and Methods Pub Date : 2016-10-12 DOI:10.1080/15376516.2016.1216208

Ching-Kai Su, C. Chou, Ko-Long Lin, Wei-Zhe Liang, Jin‐shiung Cheng, Hong‐Tai Chang, I. Chen, T. Lu, C. Kuo, Chia-Cheng Yu, Pochuen Shieh, D. Kuo, Fu-An Chen, C. Jan

{"title":"Effect of protriptyline on [Ca2+]i and viability in MG63 human osteosarcoma cells","authors":"Ching-Kai Su, C. Chou, Ko-Long Lin, Wei-Zhe Liang, Jin‐shiung Cheng, Hong‐Tai Chang, I. Chen, T. Lu, C. Kuo, Chia-Cheng Yu, Pochuen Shieh, D. Kuo, Fu-An Chen, C. Jan","doi":"10.1080/15376516.2016.1216208","DOIUrl":null,"url":null,"abstract":"Abstract Tricyclic antidepressants (TCA) have been clinically prescribed in the auxiliary treatment of cancer patients. Although protriptyline, a type of TCA, was used primarily in the clinical treatment of mood disorders in cancer patients, the effect of protriptyline on physiology in human osteosarcoma is unknown. This study examined the effect of protriptyline on cytosolic free Ca2+ concentrations ([Ca2+]i) and viability in MG63 human osteosarcoma cells. Protriptyline between 50 and 250 μM evoked [Ca2+]i rises concentration-dependently. Protriptyline induced influx of Mn2+, indirectly implicating Ca2+ influx. Protriptyline-evoked Ca2+ entry was inhibited by nifedipine by 20% but was not altered by econazole, SKF96365, GF109203X, and phorbol-12-myristate-13-acetate (PMA). In Ca2+-free medium, treatment with protriptyline inhibited the endoplasmic reticulum Ca2+ pump inhibitor thapsigargin-evoked [Ca2+]i rises. Conversely, treatment with thapsigargin inhibited 45% of protriptyline-evoked [Ca2+]i rises. Inhibition of phospholipase C (PLC) with U73122 failed to alter protriptyline-evoked [Ca2+]i rises. Protriptyline at 50–250 μM decreased cell viability, which was not reversed by pretreatment with the Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester (BAPTA/AM). Collectively, our data suggest that in MG63 cells, protriptyline induced [Ca2+]i rises by evoking Ca2+ release from the endoplasmic reticulum and other stores in a PLC-independent manner, and Ca2+ entry via a nifedipine-sensitive Ca2+ pathway. Protriptyline also caused Ca2+-independent cell death.","PeriodicalId":49117,"journal":{"name":"Toxicology Mechanisms and Methods","volume":"26 1","pages":"580 - 587"},"PeriodicalIF":2.8000,"publicationDate":"2016-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/15376516.2016.1216208","citationCount":"1","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Toxicology Mechanisms and Methods","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/15376516.2016.1216208","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"TOXICOLOGY","Score":null,"Total":0}

引用次数: 1

Abstract

Abstract Tricyclic antidepressants (TCA) have been clinically prescribed in the auxiliary treatment of cancer patients. Although protriptyline, a type of TCA, was used primarily in the clinical treatment of mood disorders in cancer patients, the effect of protriptyline on physiology in human osteosarcoma is unknown. This study examined the effect of protriptyline on cytosolic free Ca2+ concentrations ([Ca2+]i) and viability in MG63 human osteosarcoma cells. Protriptyline between 50 and 250 μM evoked [Ca2+]i rises concentration-dependently. Protriptyline induced influx of Mn2+, indirectly implicating Ca2+ influx. Protriptyline-evoked Ca2+ entry was inhibited by nifedipine by 20% but was not altered by econazole, SKF96365, GF109203X, and phorbol-12-myristate-13-acetate (PMA). In Ca2+-free medium, treatment with protriptyline inhibited the endoplasmic reticulum Ca2+ pump inhibitor thapsigargin-evoked [Ca2+]i rises. Conversely, treatment with thapsigargin inhibited 45% of protriptyline-evoked [Ca2+]i rises. Inhibition of phospholipase C (PLC) with U73122 failed to alter protriptyline-evoked [Ca2+]i rises. Protriptyline at 50–250 μM decreased cell viability, which was not reversed by pretreatment with the Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester (BAPTA/AM). Collectively, our data suggest that in MG63 cells, protriptyline induced [Ca2+]i rises by evoking Ca2+ release from the endoplasmic reticulum and other stores in a PLC-independent manner, and Ca2+ entry via a nifedipine-sensitive Ca2+ pathway. Protriptyline also caused Ca2+-independent cell death.

查看原文本刊更多论文

前列替林对MG63人骨肉瘤细胞[Ca2+]i和活力的影响

摘要三环类抗抑郁药(TCA)在临床上已被应用于癌症患者的辅助治疗。虽然proprotyline是一种TCA，主要用于癌症患者情绪障碍的临床治疗，但proprotyline对人骨肉瘤的生理影响尚不清楚。本研究检测了proprotyline对MG63人骨肉瘤细胞胞浆游离Ca2+浓度([Ca2+]i)和活力的影响。50 ~ 250 μM之间的protrityline诱导[Ca2+]i呈浓度依赖性升高。proprotyline诱导Mn2+内流，间接暗示Ca2+内流。丙替林诱导的Ca2+进入被硝苯地平抑制了20%，但被econazole、SKF96365、GF109203X和phorbl -12-肉豆蔻酸-13-乙酸酯(PMA)没有改变。在无Ca2+的培养基中，用protrityline处理可以抑制内质网Ca2+泵抑制剂thapsigargin诱发的[Ca2+]i升高。相反，用thapsigargin治疗可以抑制45%的proprotyline诱发的[Ca2+]i升高。U73122抑制磷脂酶C (PLC)不能改变丙氨酸诱发的[Ca2+]i升高。50-250 μM的Protriptyline降低了细胞活力，Ca2+螯合剂1,2-双(2-氨基苯氧基)乙烷-N,N,N'，N'-四乙酸-乙酰氧基甲酯(BAPTA/AM)预处理不能逆转这一趋势。总的来说，我们的数据表明，在MG63细胞中，protrityline通过以plc独立的方式唤醒内质网和其他储存的Ca2+释放，并通过硝苯地平敏感的Ca2+途径诱导Ca2+进入，从而诱导[Ca2+]i升高。前列替林也引起Ca2+非依赖性细胞死亡。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Toxicology Mechanisms and Methods TOXICOLOGY-

自引率

3.10%

发文量

期刊介绍： Toxicology Mechanisms and Methods is a peer-reviewed journal whose aim is twofold. Firstly, the journal contains original research on subjects dealing with the mechanisms by which foreign chemicals cause toxic tissue injury. Chemical substances of interest include industrial compounds, environmental pollutants, hazardous wastes, drugs, pesticides, and chemical warfare agents. The scope of the journal spans from molecular and cellular mechanisms of action to the consideration of mechanistic evidence in establishing regulatory policy. Secondly, the journal addresses aspects of the development, validation, and application of new and existing laboratory methods, techniques, and equipment. A variety of research methods are discussed, including: In vivo studies with standard and alternative species In vitro studies and alternative methodologies Molecular, biochemical, and cellular techniques Pharmacokinetics and pharmacodynamics Mathematical modeling and computer programs Forensic analyses Risk assessment Data collection and analysis.