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

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