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

Title
A synthetic cryptochrome inhibitor induces anti-proliferative effects and increases chemosensitivity in human breast cancer cells
Authors
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
2015-11-13
Citation
Biochemical and Biophysical Research Communications, 467(2), 441-446
Type
Article
Article Type
Article
Keywords
Antagonists and InhibitorsAnti-Tumor ActivityAntibody SpecificityAntineoplastic AgentAntineoplastic AgentsAntineoplastic AlkaloidAntiproliferative ActivityApoptosisBreast CancerCell CycleCell Cycle RegulationCell GrowthCell SurvivalChemosensitivityCircadian RhythmClock ProteinsConcentration (Parameters)Controlled StudyCryptochromeCryptochrome InhibitorCryptochromesDoxorubicinDrug EffectsDrug ResistanceDrug Resistance, NeoplasmE Box ElementFemaleGene Expression RegulationGene Expression Regulation, NeoplasticGenetic TranscriptionGeneticsHumanHuman CellHumansIC50Ks 15MCF-7 CellsMCF 7 Cell LineMessenger RNAMetabolismMolecular LibraryOrgan SpecificityPharmacologyPriority JournalSignal TransductionSmall MoleculeSmall Molecule LibrariesTamoxifenTranscription Factor ClockUnclassified Drug
ISSN
0006-291X
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. © 2015 Elsevier Inc. All rights reserved.
URI
http://hdl.handle.net/20.500.11750/2578
DOI
10.1016/j.bbrc.2015.09.103
Publisher
Academic Press Inc.
Files:
There are no files associated with this item.
Collection:
Brain and Cognitive SciencesETC1. Journal Articles


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