2. Academic Validation
  3. A synthetic cryptochrome inhibitor induces anti-proliferative effects and increases chemosensitivity in human breast cancer cells

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

  • Biochem Biophys Res Commun. 2015 Nov 13;467(2):441-6. doi: 10.1016/j.bbrc.2015.09.103.
Sung Kook Chun 1,  Sooyoung Chung 2,  Hee-Dae Kim 3,  Ju Hyung Lee 4,  Jaebong Jang 5,  Jeongah Kim 1,  Doyeon Kim 1,  Gi Hoon Son 6,  Young J Oh 4,  Young-Ger Suh 5,  Cheol Soon Lee 7,  Kyungjin Kim 8
Affiliations

Affiliations

  • 1 Department of Brain & Cognitive Sciences, Daegu-Gyeongbuk Institute of Science & Technology, Daegu, 711-873, South Korea; Department of Biological Sciences, Seoul National University, Seoul, 151-747, South Korea; Department of Brain & Cognitive Sciences, Seoul National University, Seoul, 151-747, South Korea.
  • 2 Department of Biological Sciences, Seoul National University, Seoul, 151-747, South Korea; Department of Biomedical Sciences, College of Medicine, Korea University, Seoul, 136-705, South Korea.
  • 3 Department of Biological Sciences, Seoul National University, Seoul, 151-747, South Korea.
  • 4 Department of Systems Biology, Yonsei University College of Life Science and Biotechnology, Seoul 120-749, South Korea.
  • 5 College of Pharmacy, Seoul National University, Seoul, 151-742, South Korea.
  • 6 Department of Biomedical Sciences, College of Medicine, Korea University, Seoul, 136-705, South Korea.
  • 7 Gachon Clinical Trials Center, Gachon University, Incheon, 417-842, South Korea.
  • 8 Department of Brain & Cognitive Sciences, Daegu-Gyeongbuk Institute of Science & Technology, Daegu, 711-873, South Korea; Department of Biological Sciences, Seoul National University, Seoul, 151-747, South Korea; Department of Brain & Cognitive Sciences, Seoul National University, Seoul, 151-747, South Korea. Electronic address: kyungjin@dgist.ac.kr.
PMID: 26407844 DOI: 10.1016/j.bbrc.2015.09.103
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.

Keywords

Anti-tumor activity; Breast cancer; Cryptochrome; Small molecule.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-115672
    99.40%, Cryptochrome Inhibitor