A synthetic cryptochrome inhibitor induces anti-proliferative effects and increases chemosensitivity in human breast cancer cells

Sung Kook Chun, Sooyoung Chung, Hee Dae Kim, Ju Hyung Lee, Jaebong Jang, Jeongah Kim, Doyeon Kim, Gi Hoon Son, Young J. Oh, Young Ger Suh, Cheol Soon Lee, Kyungjin Kim

Research output: Contribution to journalArticlepeer-review

38 Citations (Scopus)


Disruption of circadian rhythm is a major cause of breast cancer in humans. Cryptochrome (CRY), a circadian transcription factor, is a risk factor for initiation of breast cancer, and it is differentially expressed between normal and breast cancer tissues. Here, we evaluated the anti-proliferative and pro-apoptotic activity of KS15, a recently discovered small-molecule inhibitor of CRY, in human breast cancer cells. First, we investigated whether KS15 treatment could promote E-box-mediated transcription by inhibiting the activity of CRY in MCF-7 human breast cancer cells. Protein and mRNA levels of regulators of cell cycle and apoptosis, as well as core clock genes, were differentially modulated in response to KS15. Next, we investigated whether KS15 could inhibit proliferation and increase sensitivity to anti-tumor drugs in MCF-7 cells. We found that KS15 decreased the speed of cell growth and increased the chemosensitivity of MCF-7 cells to doxorubicin and tamoxifen, but had no effect on MCF-10A cells. These findings suggested that pharmacological inhibition of CRY by KS15 exerts an anti-proliferative effect and increases sensitivity to anti-tumor drugs in a specific type of breast cancer.

Original languageEnglish
Pages (from-to)441-446
Number of pages6
JournalBiochemical and biophysical research communications
Issue number2
Publication statusPublished - 2015 Nov 13

Bibliographical note

Funding Information:
This study was supported by grants of the Korea Healthcare Technology R&D project from the Ministry for Health & Welfare Affairs , Republic of Korea ( A121549-1201-0000100 ) and the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT, & Future Planning ( NRF-2013M3C7A1056731 ). This work was also supported by the DGIST MIREBraiN Program of the Ministry of Science, ICT, & Future Planning.

Publisher Copyright:
© 2015 Elsevier Inc. All rights reserved.


  • Anti-tumor activity
  • Breast cancer
  • Cryptochrome
  • Small molecule

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


Dive into the research topics of 'A synthetic cryptochrome inhibitor induces anti-proliferative effects and increases chemosensitivity in human breast cancer cells'. Together they form a unique fingerprint.

Cite this