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.
|Number of pages||6|
|Journal||Biochemical and Biophysical Research Communications|
|Publication status||Published - 2015 Nov 13|
Bibliographical noteFunding 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.
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology