A synthetic cryptochrome inhibitor induces anti-proliferative effects and increases chemosensitivity in human breast cancer cells
| Autor: | Young-Ger Suh, Cheol Soon Lee, Juhyung Lee, Gi Hoon Son, Sung Kook Chun, Doyeon Kim, Jeong Ah Kim, Young J. Oh, Sooyoung Chung, Kyungjin Kim, Jaebong Jang, Hee Dae Kim |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Cell Survival
Biophysics CLOCK Proteins Antineoplastic Agents Apoptosis Biology Biochemistry Small Molecule Libraries Breast cancer medicine Humans skin and connective tissue diseases Molecular Biology Transcription factor Cell growth Cell Cycle Cell Biology Cell cycle medicine.disease Circadian Rhythm Cryptochromes Gene Expression Regulation Neoplastic CLOCK Tamoxifen Doxorubicin Drug Resistance Neoplasm Organ Specificity Cancer cell MCF-7 Cells Cancer research Female Signal Transduction medicine.drug |
| Zdroj: | Biochemical and Biophysical Research Communications. 467:441-446 |
| ISSN: | 0006-291X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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