Tags

Type your tag names separated by a space and hit enter

Desipramine-induced apoptosis in human PC3 prostate cancer cells: activation of JNK kinase and caspase-3 pathways and a protective role of [Ca2+]i elevation.
Toxicology. 2008 Aug 19; 250(1):9-14.T

Abstract

The antidepressant desipramine has been shown to induce a rise in cytosolic Ca2+ levels ([Ca2+]i) and cytotoxicity in human PC3 prostate cancer cells, but the mechanisms underlying its cytotoxic effect is unclear. Cell viability was examined by WST-1 assays. Apoptosis was assessed by propidium iodide staining and an increase in caspase-3 activation. Phosphorylation of protein kinases was analyzed by immunoblotting. Desipramine caused cell death via apoptosis in a concentration-dependent manner. Immunoblotting data revealed that desipramine activated the phosphorylation of c-Jun NH2-terminal kinase (JNK), but not extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK). SP600125 (a selective JNK inhibitor) partially prevented cells from apoptosis. Pretreatment with BAPTA/AM, a Ca2+ chelator, to prevent desipramine-induced [Ca2+]i rises worsened desipramine-induced cytotoxicity. Immunoblotting data suggest that BAPTA/AM pretreatment enhanced desipramine-evoked JNK phosphorylation and caspase-3 cleavage. The results suggest that in PC3 cells, desipramine caused apoptosis via inducing JNK-associated caspase-3 activation, and [Ca2+]i rises may slow down or alleviate desipramine-induced cytotoxicity.

Authors+Show Affiliations

Department of Urology, College of Medicine, National Taiwan University, Taipei 100, Taiwan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18606486

Citation

Chang, Hong-Chiang, et al. "Desipramine-induced Apoptosis in Human PC3 Prostate Cancer Cells: Activation of JNK Kinase and Caspase-3 Pathways and a Protective Role of [Ca2+]i Elevation." Toxicology, vol. 250, no. 1, 2008, pp. 9-14.
Chang HC, Huang CC, Huang CJ, et al. Desipramine-induced apoptosis in human PC3 prostate cancer cells: activation of JNK kinase and caspase-3 pathways and a protective role of [Ca2+]i elevation. Toxicology. 2008;250(1):9-14.
Chang, H. C., Huang, C. C., Huang, C. J., Cheng, J. S., Liu, S. I., Tsai, J. Y., Chang, H. T., Huang, J. K., Chou, C. T., & Jan, C. R. (2008). Desipramine-induced apoptosis in human PC3 prostate cancer cells: activation of JNK kinase and caspase-3 pathways and a protective role of [Ca2+]i elevation. Toxicology, 250(1), 9-14. https://doi.org/10.1016/j.tox.2008.05.010
Chang HC, et al. Desipramine-induced Apoptosis in Human PC3 Prostate Cancer Cells: Activation of JNK Kinase and Caspase-3 Pathways and a Protective Role of [Ca2+]i Elevation. Toxicology. 2008 Aug 19;250(1):9-14. PubMed PMID: 18606486.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Desipramine-induced apoptosis in human PC3 prostate cancer cells: activation of JNK kinase and caspase-3 pathways and a protective role of [Ca2+]i elevation. AU - Chang,Hong-Chiang, AU - Huang,Chorng-Chih, AU - Huang,Chun-Jen, AU - Cheng,Jin-Shiung, AU - Liu,Shiuh-In, AU - Tsai,Jeng-Yu, AU - Chang,Hong-Tai, AU - Huang,Jong-Khing, AU - Chou,Chiang-Ting, AU - Jan,Chung-Ren, Y1 - 2008/05/27/ PY - 2008/03/11/received PY - 2008/05/15/revised PY - 2008/05/15/accepted PY - 2008/7/9/pubmed PY - 2008/9/13/medline PY - 2008/7/9/entrez SP - 9 EP - 14 JF - Toxicology JO - Toxicology VL - 250 IS - 1 N2 - The antidepressant desipramine has been shown to induce a rise in cytosolic Ca2+ levels ([Ca2+]i) and cytotoxicity in human PC3 prostate cancer cells, but the mechanisms underlying its cytotoxic effect is unclear. Cell viability was examined by WST-1 assays. Apoptosis was assessed by propidium iodide staining and an increase in caspase-3 activation. Phosphorylation of protein kinases was analyzed by immunoblotting. Desipramine caused cell death via apoptosis in a concentration-dependent manner. Immunoblotting data revealed that desipramine activated the phosphorylation of c-Jun NH2-terminal kinase (JNK), but not extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK). SP600125 (a selective JNK inhibitor) partially prevented cells from apoptosis. Pretreatment with BAPTA/AM, a Ca2+ chelator, to prevent desipramine-induced [Ca2+]i rises worsened desipramine-induced cytotoxicity. Immunoblotting data suggest that BAPTA/AM pretreatment enhanced desipramine-evoked JNK phosphorylation and caspase-3 cleavage. The results suggest that in PC3 cells, desipramine caused apoptosis via inducing JNK-associated caspase-3 activation, and [Ca2+]i rises may slow down or alleviate desipramine-induced cytotoxicity. SN - 0300-483X UR - https://www.unboundmedicine.com/medline/citation/18606486/Desipramine_induced_apoptosis_in_human_PC3_prostate_cancer_cells:_activation_of_JNK_kinase_and_caspase_3_pathways_and_a_protective_role_of_[Ca2+]i_elevation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0300-483X(08)00239-4 DB - PRIME DP - Unbound Medicine ER -