Tags

Type your tag names separated by a space and hit enter

Ketoconazole-induced JNK phosphorylation and subsequent cell death via apoptosis in human osteosarcoma cells.
Toxicol In Vitro. 2009 Oct; 23(7):1268-76.TV

Abstract

This study examined the effect of ketoconazole on viability, apoptosis, mitogen-activated protein kinases (MAPKs) and Ca(2+) levels in MG63 osteosarcoma cells. Ketoconazole at 20-200 microM decreased cell viability via apoptosis as demonstrated by propidium iodide staining and activation of caspase-3. Immunoblotting suggested that ketoconazole induced phosphorylation of ERK and JNK, but not p38, MAPKs. Ketoconazole-induced cell death and apoptosis were partially reversed by the selective JNK inhibitor SP600125, but not by the selective ERK inhibitor PD98059, suggesting that ketoconazole's cytotoxic action was via JNK, but not via ERK and p38 MAPKs. Ketoconazole at a concentration of 100 microM induced [Ca(2+)](i) increases. Chelation of intracellular Ca(2+) with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) totally inhibited ketoconazole-induced [Ca(2+)](i) increases without reversing ketoconazole-induced cell death. Collectively, in MG63 cells, ketoconazole induced cell death and apoptosis via evoking JNK phosphorylation in a Ca(2+)-independent manner.

Authors+Show Affiliations

Department of Rehabilitation, Kaohsiung Veterans General Hospital, 813 Kaohsiung, Taiwan.No 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

19631732

Citation

Lin, Ko-Long, et al. "Ketoconazole-induced JNK Phosphorylation and Subsequent Cell Death Via Apoptosis in Human Osteosarcoma Cells." Toxicology in Vitro : an International Journal Published in Association With BIBRA, vol. 23, no. 7, 2009, pp. 1268-76.
Lin KL, Huang CC, Cheng JS, et al. Ketoconazole-induced JNK phosphorylation and subsequent cell death via apoptosis in human osteosarcoma cells. Toxicol In Vitro. 2009;23(7):1268-76.
Lin, K. L., Huang, C. C., Cheng, J. S., Tsai, J. Y., Lu, Y. C., Chang, H. T., & Jan, C. R. (2009). Ketoconazole-induced JNK phosphorylation and subsequent cell death via apoptosis in human osteosarcoma cells. Toxicology in Vitro : an International Journal Published in Association With BIBRA, 23(7), 1268-76. https://doi.org/10.1016/j.tiv.2009.07.025
Lin KL, et al. Ketoconazole-induced JNK Phosphorylation and Subsequent Cell Death Via Apoptosis in Human Osteosarcoma Cells. Toxicol In Vitro. 2009;23(7):1268-76. PubMed PMID: 19631732.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ketoconazole-induced JNK phosphorylation and subsequent cell death via apoptosis in human osteosarcoma cells. AU - Lin,Ko-Long, AU - Huang,Chorng-Chih, AU - Cheng,Jin-Shiung, AU - Tsai,Jeng-Yu, AU - Lu,Yih-Chau, AU - Chang,Hong-Tai, AU - Jan,Chung-Ren, Y1 - 2009/07/23/ PY - 2008/11/11/received PY - 2009/06/17/revised PY - 2009/07/17/accepted PY - 2009/7/28/entrez PY - 2009/7/28/pubmed PY - 2009/12/16/medline SP - 1268 EP - 76 JF - Toxicology in vitro : an international journal published in association with BIBRA JO - Toxicol In Vitro VL - 23 IS - 7 N2 - This study examined the effect of ketoconazole on viability, apoptosis, mitogen-activated protein kinases (MAPKs) and Ca(2+) levels in MG63 osteosarcoma cells. Ketoconazole at 20-200 microM decreased cell viability via apoptosis as demonstrated by propidium iodide staining and activation of caspase-3. Immunoblotting suggested that ketoconazole induced phosphorylation of ERK and JNK, but not p38, MAPKs. Ketoconazole-induced cell death and apoptosis were partially reversed by the selective JNK inhibitor SP600125, but not by the selective ERK inhibitor PD98059, suggesting that ketoconazole's cytotoxic action was via JNK, but not via ERK and p38 MAPKs. Ketoconazole at a concentration of 100 microM induced [Ca(2+)](i) increases. Chelation of intracellular Ca(2+) with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) totally inhibited ketoconazole-induced [Ca(2+)](i) increases without reversing ketoconazole-induced cell death. Collectively, in MG63 cells, ketoconazole induced cell death and apoptosis via evoking JNK phosphorylation in a Ca(2+)-independent manner. SN - 1879-3177 UR - https://www.unboundmedicine.com/medline/citation/19631732/Ketoconazole_induced_JNK_phosphorylation_and_subsequent_cell_death_via_apoptosis_in_human_osteosarcoma_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0887-2333(09)00197-0 DB - PRIME DP - Unbound Medicine ER -