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

Sung Kook Chun, Sooyoung Chung, Hee Dae Kim, Ju Hyung Lee, Jaebong Jang, Jeongah Kim, Doyeon Kim, Gi Hoon Son, Young J. Oh, Young Ger Suh, Cheol Soon Lee, Kyungjin Kim

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)441-446
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume467
Issue number2
DOIs
Publication statusPublished - 2015 Nov 13

Fingerprint

Cryptochromes
Cells
Breast Neoplasms
Tumors
MCF-7 Cells
Peptide Initiation Factors
Cell growth
Tamoxifen
Transcription
Pharmaceutical Preparations
Doxorubicin
Clocks
Transcription Factors
Genes
Tissue
Apoptosis
Circadian Rhythm
Messenger RNA
Molecules
Neoplasms

Keywords

  • Anti-tumor activity
  • Breast cancer
  • Cryptochrome
  • Small molecule

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

Cite this

A synthetic cryptochrome inhibitor induces anti-proliferative effects and increases chemosensitivity in human breast cancer cells. / Chun, Sung Kook; Chung, Sooyoung; Kim, Hee Dae; Lee, Ju Hyung; Jang, Jaebong; Kim, Jeongah; Kim, Doyeon; Son, Gi Hoon; Oh, Young J.; Suh, Young Ger; Lee, Cheol Soon; Kim, Kyungjin.

In: Biochemical and Biophysical Research Communications, Vol. 467, No. 2, 13.11.2015, p. 441-446.

Research output: Contribution to journalArticle

Chun, Sung Kook ; Chung, Sooyoung ; Kim, Hee Dae ; Lee, Ju Hyung ; Jang, Jaebong ; Kim, Jeongah ; Kim, Doyeon ; Son, Gi Hoon ; Oh, Young J. ; Suh, Young Ger ; Lee, Cheol Soon ; Kim, Kyungjin. / A synthetic cryptochrome inhibitor induces anti-proliferative effects and increases chemosensitivity in human breast cancer cells. In: Biochemical and Biophysical Research Communications. 2015 ; Vol. 467, No. 2. pp. 441-446.
@article{cd01f1833d0d45b5858dc93be96e2080,
title = "A synthetic cryptochrome inhibitor induces anti-proliferative effects and increases chemosensitivity in human breast cancer cells",
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",
author = "Chun, {Sung Kook} and Sooyoung Chung and Kim, {Hee Dae} and Lee, {Ju Hyung} and Jaebong Jang and Jeongah Kim and Doyeon Kim and Son, {Gi Hoon} and Oh, {Young J.} and Suh, {Young Ger} and Lee, {Cheol Soon} and Kyungjin Kim",
year = "2015",
month = "11",
day = "13",
doi = "10.1016/j.bbrc.2015.09.103",
language = "English",
volume = "467",
pages = "441--446",
journal = "The BMJ",
issn = "0730-6512",
publisher = "Kluwer Academic Publishers",
number = "2",

}

TY - JOUR

T1 - A synthetic cryptochrome inhibitor induces anti-proliferative effects and increases chemosensitivity in human breast cancer cells

AU - Chun, Sung Kook

AU - Chung, Sooyoung

AU - Kim, Hee Dae

AU - Lee, Ju Hyung

AU - Jang, Jaebong

AU - Kim, Jeongah

AU - Kim, Doyeon

AU - Son, Gi Hoon

AU - Oh, Young J.

AU - Suh, Young Ger

AU - Lee, Cheol Soon

AU - Kim, Kyungjin

PY - 2015/11/13

Y1 - 2015/11/13

N2 - 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.

AB - 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.

KW - Anti-tumor activity

KW - Breast cancer

KW - Cryptochrome

KW - Small molecule

UR - http://www.scopus.com/inward/record.url?scp=84944398037&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84944398037&partnerID=8YFLogxK

U2 - 10.1016/j.bbrc.2015.09.103

DO - 10.1016/j.bbrc.2015.09.103

M3 - Article

VL - 467

SP - 441

EP - 446

JO - The BMJ

JF - The BMJ

SN - 0730-6512

IS - 2

ER -