Page 158 - ebook

[B. Cell Biology/Stem Cell] B-14

Inhibition of JNK1 signaling by Indirubin-3-monoxime

prevents tumorigenesis in breast cancer

Hyung-Ju Lee¹, Mi-Yeon Kim¹, Eun-Hye Jo¹, So-I Noh¹, Hee-Sae Park¹*

¹School of Biological Sciences and Technology, Chonnam National University, Gwangju 61186, Korea

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.