title: Effect of protriptyline on [Ca2+]iand viability in MG63 human osteosarcoma cells.
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+]irises 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+]irises. Conversely, treatment with thapsigargin inhibited 45% of protriptyline-evoked [Ca2+]irises. Inhibition of phospholipase C (PLC) with U73122 failed to alter protriptyline-evoked [Ca2+]irises. 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+]irises 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.
authors: a Department of Medicine , Kaohsiung Veterans General Hospital Pingtung Branch , Pingtung , Taiwan.
authors: Ching-Kai
authors: CK
authors: Su
authors: 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: Chiang-Ting
authors: CT
authors: Chou
authors: d Department of Rehabilitation , Kaohsiung Veterans General Hospital Tainan Branch , Tainan , Taiwan.
authors: Ko-Long
authors: KL
authors: Lin
authors: e Department of Medical Education and Research , Kaohsiung Veterans General Hospital , Kaohsiung , Taiwan.
authors: Wei-Zhe
authors: WZ
authors: Liang
authors: f Department of Medicine , Kaohsiung Veterans General Hospital , Kaohsiung , Taiwan.
authors: Jin-Shiung
authors: JS
authors: Cheng
authors: g Department of Surgery , Kaohsiung Veterans General Hospital , Kaohsiung , Taiwan.
authors: Hong-Tai
authors: HT
authors: Chang
authors: g Department of Surgery , Kaohsiung Veterans General Hospital , Kaohsiung , Taiwan.
authors: I-Shu
authors: IS
authors: Chen
authors: h Department of Psychiatry , Kaohsiung Veterans General Hospital , Kaohsiung , Taiwan.
authors: Ti
authors: T
authors: Lu
authors: i Department of Nursing , Tzu Hui Institute of Technology , Pingtung , Taiwan.
authors: Chun-Chi
authors: CC
authors: Kuo
authors: g Department of Surgery , Kaohsiung Veterans General Hospital , Kaohsiung , Taiwan.
authors: Chia-Cheng
authors: CC
authors: Yu
authors: j Department of Pharmacy , Tajen University , Pingtung , Taiwan.
authors: Pochuen
authors: P
authors: Shieh
authors: j Department of Pharmacy , Tajen University , Pingtung , Taiwan.
authors: Daih-Huang
authors: DH
authors: Kuo
authors: j Department of Pharmacy , Tajen University , Pingtung , Taiwan.
authors: Fu-An
authors: FA
authors: Chen
authors: e Department of Medical Education and Research , Kaohsiung Veterans General Hospital , Kaohsiung , Taiwan.
authors: Chung-Ren
authors: CR
authors: Jan
mesh_terms: D000929:Antidepressive Agents, Tricyclic / Q000633:toxicity*; D002118:Calcium / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011530:Protriptyline / Q000633:toxicity*
chemical_list: D000929:Antidepressive Agents, Tricyclic; D011530:Protriptyline; D002118:Calcium
keywords: Ca2+; endoplasmic reticulum; human osteosarcoma cells; protriptyline