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

Ching Kai Su, Chiang Ting Chou, Ko Long Lin, Wei Zhe Liang, Jin Shiung Cheng, Hong Tai Chang, I. Shu Chen, Ti Lu, Chun Chi Kuo, Chia Cheng Yu, Pochuen Shieh, Daih Huang Kuo, Fu An Chen, Chung Ren Jan*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

2 Scopus citations

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.

Original languageEnglish
Pages (from-to)580-587
Number of pages8
JournalToxicology Mechanisms and Methods
Volume26
Issue number8
DOIs
StatePublished - 12 10 2016
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2016 Informa UK Limited, trading as Taylor & Francis Group.

Keywords

  • Ca2
  • endoplasmic reticulum
  • human osteosarcoma cells
  • protriptyline

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