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

Abstract

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. - Highlights: • Cryptochrome inhibitor (KS15) has anti-tumor activity to human breast cancer cells. • KS15 induces differential changes in cellmore » cycle regulators and pro-apoptotic genes. • KS15 inhibits MCF-7 cell growth and enhances susceptibility to anti-tumor drugs.« less

Authors:
 [1];  [2];  [2];  [3];  [4]; ;  [1];  [5];  [3];  [4];  [6];
  1. Department of Brain & Cognitive Sciences, Daegu-Gyeongbuk Institute of Science & Technology, Daegu, 711-873 (Korea, Republic of)
  2. Department of Biological Sciences, Seoul National University, Seoul, 151-747 (Korea, Republic of)
  3. Department of Systems Biology, Yonsei University College of Life Science and Biotechnology, Seoul 120-749 (Korea, Republic of)
  4. College of Pharmacy, Seoul National University, Seoul, 151-742 (Korea, Republic of)
  5. Department of Biomedical Sciences, College of Medicine, Korea University, Seoul, 136-705 (Korea, Republic of)
  6. Gachon Clinical Trials Center, Gachon University, Incheon, 417-842 (Korea, Republic of)
Publication Date:
OSTI Identifier:
22592805
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 467; Journal Issue: 2; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANIMAL TISSUES; APOPTOSIS; CELL CYCLE; CELL PROLIFERATION; DOXORUBICIN; GENES; INHIBITION; MAMMARY GLANDS; MESSENGER-RNA; NEOPLASMS; SENSITIVITY; TAMOXIFEN; TRANSCRIPTION; TRANSCRIPTION FACTORS

Citation Formats

Chun, Sung Kook, Department of Biological Sciences, Seoul National University, Seoul, 151-747, Department of Brain & Cognitive Sciences, Seoul National University, Seoul, 151-747, Chung, Sooyoung, Department of Biomedical Sciences, College of Medicine, Korea University, Seoul, 136-705, Kim, Hee-Dae, Lee, Ju Hyung, Jang, Jaebong, Kim, Jeongah, Kim, Doyeon, Department of Biological Sciences, Seoul National University, Seoul, 151-747, Department of Brain & Cognitive Sciences, Seoul National University, Seoul, 151-747, Son, Gi Hoon, Oh, Young J., Suh, Young-Ger, Lee, Cheol Soon, and others, and. A synthetic cryptochrome inhibitor induces anti-proliferative effects and increases chemosensitivity in human breast cancer cells. United States: N. p., 2015. Web. doi:10.1016/J.BBRC.2015.09.103.
Chun, Sung Kook, Department of Biological Sciences, Seoul National University, Seoul, 151-747, Department of Brain & Cognitive Sciences, Seoul National University, Seoul, 151-747, Chung, Sooyoung, Department of Biomedical Sciences, College of Medicine, Korea University, Seoul, 136-705, Kim, Hee-Dae, Lee, Ju Hyung, Jang, Jaebong, Kim, Jeongah, Kim, Doyeon, Department of Biological Sciences, Seoul National University, Seoul, 151-747, Department of Brain & Cognitive Sciences, Seoul National University, Seoul, 151-747, Son, Gi Hoon, Oh, Young J., Suh, Young-Ger, Lee, Cheol Soon, & others, and. A synthetic cryptochrome inhibitor induces anti-proliferative effects and increases chemosensitivity in human breast cancer cells. United States. https://doi.org/10.1016/J.BBRC.2015.09.103
Chun, Sung Kook, Department of Biological Sciences, Seoul National University, Seoul, 151-747, Department of Brain & Cognitive Sciences, Seoul National University, Seoul, 151-747, Chung, Sooyoung, Department of Biomedical Sciences, College of Medicine, Korea University, Seoul, 136-705, Kim, Hee-Dae, Lee, Ju Hyung, Jang, Jaebong, Kim, Jeongah, Kim, Doyeon, Department of Biological Sciences, Seoul National University, Seoul, 151-747, Department of Brain & Cognitive Sciences, Seoul National University, Seoul, 151-747, Son, Gi Hoon, Oh, Young J., Suh, Young-Ger, Lee, Cheol Soon, and others, and. 2015. "A synthetic cryptochrome inhibitor induces anti-proliferative effects and increases chemosensitivity in human breast cancer cells". United States. https://doi.org/10.1016/J.BBRC.2015.09.103.
@article{osti_22592805,
title = {A synthetic cryptochrome inhibitor induces anti-proliferative effects and increases chemosensitivity in human breast cancer cells},
author = {Chun, Sung Kook and Department of Biological Sciences, Seoul National University, Seoul, 151-747 and Department of Brain & Cognitive Sciences, Seoul National University, Seoul, 151-747 and Chung, Sooyoung and Department of Biomedical Sciences, College of Medicine, Korea University, Seoul, 136-705 and Kim, Hee-Dae and Lee, Ju Hyung and Jang, Jaebong and Kim, Jeongah and Kim, Doyeon and Department of Biological Sciences, Seoul National University, Seoul, 151-747 and Department of Brain & Cognitive Sciences, Seoul National University, Seoul, 151-747 and Son, Gi Hoon and Oh, Young J. and Suh, Young-Ger and Lee, Cheol Soon and others, and},
abstractNote = {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. - Highlights: • Cryptochrome inhibitor (KS15) has anti-tumor activity to human breast cancer cells. • KS15 induces differential changes in cell cycle regulators and pro-apoptotic genes. • KS15 inhibits MCF-7 cell growth and enhances susceptibility to anti-tumor drugs.},
doi = {10.1016/J.BBRC.2015.09.103},
url = {https://www.osti.gov/biblio/22592805}, journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 2,
volume = 467,
place = {United States},
year = {Fri Nov 13 00:00:00 EST 2015},
month = {Fri Nov 13 00:00:00 EST 2015}
}