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A synthetic cryptochrome inhibitor induces anti-proliferative effects and increases chemosensitivity in human breast cancer cells
- Source :
- Biochemical and Biophysical Research Communications. 467:441-446
- Publication Year :
- 2015
- Publisher :
- Elsevier BV, 2015.
-
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.
- Subjects :
- 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
Subjects
Details
- ISSN :
- 0006291X
- Volume :
- 467
- Database :
- OpenAIRE
- Journal :
- Biochemical and Biophysical Research Communications
- Accession number :
- edsair.doi.dedup.....a38d761c0e28ea266c575c99f06e0e0e