JNK and ERK mitogen-activated protein kinases mediate THDA-induced apoptosis in K562 cells View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2007-10-13

AUTHORS

Sheng-Huei Yang, Zchong-Zcho Wu, Ching-Ming Chien, Yu-Hsiang Lo, Ming-Jung Wu, Long-Sen Chang, Shinne-Ren Lin

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. More... »

PAGES

291-302

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s10565-007-9038-6

DOI

http://dx.doi.org/10.1007/s10565-007-9038-6

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1030582022

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/17934787


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