title: The mechanism of protriptyline-induced Ca2+ movement and non-Ca2+-triggered cell death in PC3 human prostate cancer cells.
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 Ca(2+) movement and cell viability in PC3 human prostate cancer cells. The Ca(2+)-sensitive fluorescent dye fura-2 was used to measure [Ca(2+)](i). Protriptyline evoked [Ca(2+)](i) rises concentration-dependently. The response was reduced by removing extracellular Ca(2+). Protriptyline-evoked Ca(2+) 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 Ca(2+) pump inhibitor 2,5-di-tert-butylhydr-oquinone (BHQ) in Ca(2+)-free medium inhibited 60% of protriptyline-evoked [Ca(2+)](i) rises. Conversely, treatment with protriptyline abolished BHQ-evoked [Ca(2+)](i) rises. Inhibition of phospholipase C with U73122 suppressed 50% of protriptyline-evoked [Ca(2+)](i) rises. At concentrations of 50-70 µM, protriptyline decreased cell viability in a concentration-dependent manner; which were not reversed by chelating cytosolic Ca(2+) with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester (BAPTA/AM). Collectively, in PC3 cells, protriptyline evoked [Ca(2+)](i) rises by inducing phospholipase C-associated Ca(2+) release from the endoplasmic reticulum and other stores, and Ca(2+) influx via protein kinase C-sensitive store-operated Ca(2+) channels. Protriptyline caused cell death that was independent of [Ca(2+)](i) rises.
authors.affiliation: a Department of Surgery , Kaohsiung Veterans General Hospital , Kaohsiung , Taiwan .
authors.forename: Hong-Tai
authors.initials: HT
authors.lastname: Chang
authors.affiliation: b Department of Nursing, Division of Basic Medical Sciences , Chang Gung Institute of Technology , Chia-Yi , Taiwan .|c Chronic Diseases and Health Promotion Research Center, Chang Gung Institute of Technology , Chia-Yi , Taiwan .
authors.forename: Chiang-Ting
authors.initials: CT
authors.lastname: Chou
authors.affiliation: a Department of Surgery , Kaohsiung Veterans General Hospital , Kaohsiung , Taiwan .
authors.forename: Chia-Cheng
authors.initials: CC
authors.lastname: Yu
authors.affiliation: a Department of Surgery , Kaohsiung Veterans General Hospital , Kaohsiung , Taiwan .
authors.forename: Jeng-Yu
authors.initials: JY
authors.lastname: Tsai
authors.affiliation: d Division of Pediatrics , St. Joseph Hospital , Kaohsiung , Taiwan .
authors.forename: Te-Kung
authors.initials: TK
authors.lastname: Sun
authors.affiliation: e Department of Medical Education and Research .
authors.forename: Wei-Zhe
authors.initials: WZ
authors.lastname: Liang
authors.affiliation: f Department of Rehabilitation , and.
authors.forename: Ko-Long
authors.initials: KL
authors.lastname: Lin
authors.affiliation: g Department of Dermatology , Kaohsiung Veterans General Hospital , Kaohsiung , Taiwan .
authors.forename: Hui-Wen
authors.initials: HW
authors.lastname: Tseng
authors.affiliation: h Department of Nursing , Tzu Hui Institute of Technology , Pingtung , Taiwan .
authors.forename: Chun-Chi
authors.initials: CC
authors.lastname: Kuo
authors.affiliation: i Department of Pharmacy , Tajen University , Pingtung , Taiwan , and.
authors.forename: Fu-An
authors.initials: FA
authors.lastname: Chen
authors.affiliation: i Department of Pharmacy , Tajen University , Pingtung , Taiwan , and.
authors.forename: Daih-Huang
authors.initials: DH
authors.lastname: Kuo
authors.affiliation: j Department of Psychiatry , Kaohsiung Veterans General Hospital , Kaohsiung , Taiwan.
authors.forename: Chih-Chuan
authors.initials: CC
authors.lastname: Pan
authors.affiliation: e Department of Medical Education and Research .
authors.forename: Chin-Man
authors.initials: CM
authors.lastname: Ho
authors.affiliation: i Department of Pharmacy , Tajen University , Pingtung , Taiwan , and.
authors.forename: Pochuen
authors.initials: P
authors.lastname: Shieh
authors.affiliation: e Department of Medical Education and Research .
authors.forename: Chung-Ren
authors.initials: CR
authors.lastname: Jan
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001693:Biological Transport, Active / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D011530:Protriptyline / Q000008:administration & dosage*
chemical_list: D011530:Protriptyline; D002118:Calcium
keywords: Ca2+; endoplasmic reticulum; phospholipase C; prostate cancer cells; protriptyline; store-operated Ca2+ channels