대한의생명과학회지 (Biomedical Science Letters)

  • 제27권3호
  • /
  • Pages.134-141
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  • 2021
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  • 1738-3226(pISSN)
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  • 2288-7415(eISSN)
대한의생명과학회 (The Korean Society for Biomedical Laboratory Sciences)
권호 표지
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Indirubin-3-monoxime Prevents Tumorigenesis in Breast Cancer through Inhibition of JNK1 Activity

  • Kim, Mi-Yeon (School of Biological Sciences and Technology, Chonnam National University) ;
  • Jo, Eun-Hye (School of Biological Sciences and Technology, Chonnam National University) ;
  • Kim, Yong-Chul (School of Life Sciences, Gwangju Institute of Science & Technology) ;
  • Park, Hee-Sae (School of Biological Sciences and Technology, Chonnam National University)
  • 투고 : 2021.08.25
  • 심사 : 2021.09.14
  • 발행 : 2021.09.30
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초록

c-Jun N-terminal kinases (JNKs) have a Janus face, regulating both cell apoptosis and survival. The present study focused on understanding the function of JNK in tumor development and the chemoresistance underlying JNK-mediated cancer cell survival. We identified an inhibitor of JNK1, an important regulator of cancer cell survival. Kinase assay data showed that JNK1-dependent c-Jun phosphorylation was inhibited by indirubin derivatives. In particular, indirubin-3-monoxime (I3M) directly inhibited the phosphorylation of c-Jun in vitro, with a half inhibition dose (IC50) of 10 nM. I3M had a significant inhibitory effect on JNK1 activity. Furthermore, we carried out assays to determine the viability, migration, and proliferation of breast cancer cells. Our results demonstrated that cell growth, scratched wound healing, and colony forming abilities were inhibited by the JNK inhibitor SP600125 and I3M. The combination of SP600125 and I3M significantly decreased cancer cell proliferation, compared with either SP600125 or I3M alone. Our studies may provide further support for JNK1-targeting cancer therapy using the indirubin derivative I3M in breast cancer.

키워드

과제정보

This work was supported by the National Research Foundation of Korea (NRF) funded by the Korea government (MSIT) (No. NRF-2019R1A2C1007197). This study was financially supported by Chonnam National University (Grant number: 2016-2753). We would like to thank Editage (www.editage.co.kr) for English language editing.

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