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Research Article

The mechanism of protriptyline-induced Ca2+ movement and non-Ca2+-triggered cell death in PC3 human prostate cancer cells

, , , , , , , , , , , , , & show all
Pages 429-434 | Received 19 Aug 2014, Accepted 16 Dec 2014, Published online: 22 Jun 2015
 

Abstract

Protriptyline, a tricyclic anti-depressant, is used primarily to treat the combination of symptoms of anxiety and depression. However, the effect of protriptyline on prostate caner is unknown. This study examined whether the anti-depressant protriptyline altered Ca2+ movement and cell viability in PC3 human prostate cancer cells. The Ca2+-sensitive fluorescent dye fura-2 was used to measure [Ca2+]i. Protriptyline evoked [Ca2+]i rises concentration-dependently. The response was reduced by removing extracellular Ca2+. Protriptyline-evoked Ca2+ entry was inhibited by store-operated channel inhibitors (nifedipine, econazole and SKF96365), protein kinase C activator (phorbol 12-myristate 13 acetate, PMA) and protein kinase C inhibitor (GF109203X). Treatment with the endoplasmic reticulum Ca2+ pump inhibitor 2,5-di-tert-butylhydr-oquinone (BHQ) in Ca2+-free medium inhibited 60% of protriptyline-evoked [Ca2+]i rises. Conversely, treatment with protriptyline abolished BHQ-evoked [Ca2+]i rises. Inhibition of phospholipase C with U73122 suppressed 50% of protriptyline-evoked [Ca2+]i rises. At concentrations of 50–70 µM, protriptyline decreased cell viability in a concentration-dependent manner; which were not reversed by chelating cytosolic Ca2+ with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester (BAPTA/AM). Collectively, in PC3 cells, protriptyline evoked [Ca2+]i rises by inducing phospholipase C-associated Ca2+ release from the endoplasmic reticulum and other stores, and Ca2+ influx via protein kinase C-sensitive store-operated Ca2+ channels. Protriptyline caused cell death that was independent of [Ca2+]i rises.

Declaration of interest

This work was supported by a grant from Kaohsiung Veterans General Hospital (VGHKS 102-025) to C.-R. Jan. The authors declare no conflict of interest.

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