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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
- Chun, SK[Chun, Sung Kook]; Chung, S[Chung, Sooyoung]; Kim, HD[Kim, Hee-Dae]; Lee, JH[Lee, Ju Hyung]; Jang, J[Jang, Jaebong]; Kim, J[Kim, Jeongah]; Kim, D[Kim, Doyeon]; Son, GH[Son, Gi Hoon]; Oh, YJ[Oh, Young J.]; Suh, YG[Suh, Young-Ger]; Lee, CS[Lee, Cheol Soon]; Kim, K[Kim, Kyungjin]
- DGIST Authors
- Chun, SK[Chun, Sung Kook]; Kim, D[Kim, Doyeon]; Kim, K[Kim, Kyungjin]
- Issue Date
- Biochemical and Biophysical Research Communications, 467(2), 441-446
- Article Type
- Antagonists and Inhibitors; Anti-Tumor Activity; Antibody Specificity; Antineoplastic Agent; Antineoplastic Agents; Antineoplastic Alkaloid; Antiproliferative Activity; Apoptosis; Breast Cancer; Cell Cycle; Cell Cycle Regulation; Cell Growth; Cell Survival; Chemosensitivity; Circadian Rhythm; Clock Proteins; Concentration (Parameters); Controlled Study; Cryptochrome; Cryptochrome Inhibitor; Cryptochromes; Doxorubicin; Drug Effects; Drug Resistance; Drug Resistance, Neoplasm; E Box Element; Female; Gene Expression Regulation; Gene Expression Regulation, Neoplastic; Genetic Transcription; Genetics; Human; Human Cell; Humans; IC50; Ks 15; MCF-7 Cells; MCF 7 Cell Line; Messenger RNA; Metabolism; Molecular Library; Organ Specificity; Pharmacology; Priority Journal; Signal Transduction; Small Molecule; Small Molecule Libraries; Tamoxifen; Transcription Factor Clock; Unclassified Drug
- 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. © 2015 Elsevier Inc. All rights reserved.
- Academic Press Inc.
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