[논문]Miconazole inhibits signal transducer and activator of transcription 3 signaling by preventing its interaction with DNA damage‐induced apoptosis suppressor

Yoon, Sung‐; Hoon; Kim, Bo‐; Kyung; Kang, Mi‐; Jung; Im, Joo‐; Young; Won, Misun

doi:10.1111/cas.14432

[해외논문] Miconazole inhibits signal transducer and activator of transcription 3 signaling by preventing its interaction with DNA damage‐induced apoptosis suppressor 원문보기

Cancer Science, v.111 no.7, 2020년, pp.2499 - 2507

Yoon, Sung‐Hoon (Personalized Genomic Medicine Research Center KRIBB Daejeon Korea) , Kim, Bo‐Kyung (Personalized Genomic Medicine Research Center KRIBB Daejeon Korea) , Kang, Mi‐Jung (Personalized Genomic Medicine Research Center KRIBB Daejeon Korea) , Im, Joo‐Young (Personalized Genomic Medicine Research Center KRIBB Daejeon Korea) , Won, Misun (Personalized Genomic Medicine Research Center KRIBB Daejeon Korea)

Abstract ▼ AI-Helper

AbstractDNA damage‐induced apoptosis suppressor (DDIAS) facilitates the survival of lung cancer by suppressing apoptosis. Moreover, DDIAS promotes tyrosine phosphorylation of signal transducer and activator of transcription 3 (STAT3) via their interaction. Here, we identified miconazole as an inhibitor of DDIAS/STAT3 interaction by screening a chemical library using a yeast two‐hybrid assay. Miconazole inhibited growth, migration and invasion of lung cancer cells. Furthermore, miconazole suppressed STAT3 tyrosine Y705 phosphorylation and the expression of its target genes, such as cyclin D1, survivin and snail but had no suppressive effect on the activation of ERK1/2 or AKT, which is involved in the survival of lung cancer. As expected, no interaction between DDIAS and STAT3 occurred in the presence of miconazole, as confirmed by immunoprecipitation assays. Mouse xenograft experiments showed that miconazole significantly suppressed both tumor size and weight in an NCI‐H1703 mouse model. Tyrosine phosphorylation of STAT3 at Y705 and expression of its targets, such as cyclin D1, survivin and snail, were decreased in miconazole‐treated tumor tissues, as compared with those in vehicle‐treated tumor tissues. These data suggest that miconazole exerts an anti–cancer effect by suppressing STAT3 activation through inhibiting DDIAS/STAT3 binding.

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