Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 467, Issue 2, Pages 441-446Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2015.09.103
Keywords
Breast cancer; Cryptochrome; Small molecule; Anti-tumor activity
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Funding
- Korea Healthcare Technology R&D project from the Ministry for Health & Welfare Affairs, Republic of Korea [A121549-1201-0000100]
- National Research Foundation of Korea (NRF) - Ministry of Science, ICT, & Future Planning [NRF-2013M3C7A1056731]
- DGIST MIREBraiN Program of the Ministry of Science, ICT, & Future Planning
- National Research Foundation of Korea [2013M3C7A1056731] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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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 proapoptotic 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. (C) 2015 Elsevier Inc. All rights reserved.
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