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JNK and ERK mitogen-activated protein kinases mediate THDA-induced apoptosis in K562 cells.
Cell Biol Toxicol. 2008 Aug; 24(4):291-302.CB

Abstract

2-(6-(2-thieanisyl)-3(Z)-hexen-1, 5-diynyl) aniline (THDA), an enediyne compound, was identified in our laboratory as a novel antineoplastic agent against human leukemia K562 cells. THDA-induced apoptosis was associated with the upregulation of Bax, downregulation of X-linked inhibitor of apoptosis (XIAP), as well as the activation of caspase-3 and caspase-9. In addition, the mitogen-activated protein family kinases, including c-Jun N-terminal kinase (JNK) and extracellular signal-regulated protein kinase (ERK) kinases, and the transcription factor c-Jun were all activated by phosphorylation after 6 h exposure to THDA. Phosphorylation (activation) of JNK and ERK kinases by THDA was blocked by an ERK inhibitor, PD98059, or a JNK inhibitor, JNK-1, respectively, suggesting that THDA-induced apoptosis in K562 cells is ERK and JNK dependent. Moreover, the blockade of ERK and JNK also attenuated the modulation of Bax and XIAP, as well as the activation of caspase-3 and caspase-9 induced by THDA. These findings suggest that the activation of JNK and ERK is involved in the THDA-induced apoptosis of K562 cells. Therefore, this investigation, for the first time, uncovered the biological properties of this novel antitumor enediyne.

Authors+Show Affiliations

Faculty of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC.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

17934787

Citation

Yang, Sheng-Huei, et al. "JNK and ERK Mitogen-activated Protein Kinases Mediate THDA-induced Apoptosis in K562 Cells." Cell Biology and Toxicology, vol. 24, no. 4, 2008, pp. 291-302.
Yang SH, Wu ZZ, Chien CM, et al. JNK and ERK mitogen-activated protein kinases mediate THDA-induced apoptosis in K562 cells. Cell Biol Toxicol. 2008;24(4):291-302.
Yang, S. H., Wu, Z. Z., Chien, C. M., Lo, Y. H., Wu, M. J., Chang, L. S., & Lin, S. R. (2008). JNK and ERK mitogen-activated protein kinases mediate THDA-induced apoptosis in K562 cells. Cell Biology and Toxicology, 24(4), 291-302.
Yang SH, et al. JNK and ERK Mitogen-activated Protein Kinases Mediate THDA-induced Apoptosis in K562 Cells. Cell Biol Toxicol. 2008;24(4):291-302. PubMed PMID: 17934787.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - JNK and ERK mitogen-activated protein kinases mediate THDA-induced apoptosis in K562 cells. AU - Yang,Sheng-Huei, AU - Wu,Zchong-Zcho, AU - Chien,Ching-Ming, AU - Lo,Yu-Hsiang, AU - Wu,Ming-Jung, AU - Chang,Long-Sen, AU - Lin,Shinne-Ren, Y1 - 2007/10/13/ PY - 2007/06/11/received PY - 2007/09/22/accepted PY - 2007/10/16/pubmed PY - 2008/9/13/medline PY - 2007/10/16/entrez SP - 291 EP - 302 JF - Cell biology and toxicology JO - Cell Biol Toxicol VL - 24 IS - 4 N2 - 2-(6-(2-thieanisyl)-3(Z)-hexen-1, 5-diynyl) aniline (THDA), an enediyne compound, was identified in our laboratory as a novel antineoplastic agent against human leukemia K562 cells. THDA-induced apoptosis was associated with the upregulation of Bax, downregulation of X-linked inhibitor of apoptosis (XIAP), as well as the activation of caspase-3 and caspase-9. In addition, the mitogen-activated protein family kinases, including c-Jun N-terminal kinase (JNK) and extracellular signal-regulated protein kinase (ERK) kinases, and the transcription factor c-Jun were all activated by phosphorylation after 6 h exposure to THDA. Phosphorylation (activation) of JNK and ERK kinases by THDA was blocked by an ERK inhibitor, PD98059, or a JNK inhibitor, JNK-1, respectively, suggesting that THDA-induced apoptosis in K562 cells is ERK and JNK dependent. Moreover, the blockade of ERK and JNK also attenuated the modulation of Bax and XIAP, as well as the activation of caspase-3 and caspase-9 induced by THDA. These findings suggest that the activation of JNK and ERK is involved in the THDA-induced apoptosis of K562 cells. Therefore, this investigation, for the first time, uncovered the biological properties of this novel antitumor enediyne. SN - 0742-2091 UR - https://www.unboundmedicine.com/medline/citation/17934787/JNK_and_ERK_mitogen_activated_protein_kinases_mediate_THDA_induced_apoptosis_in_K562_cells_ L2 - https://doi.org/10.1007/s10565-007-9038-6 DB - PRIME DP - Unbound Medicine ER -