| ORIGINAL ARTICLE |
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| Year : 2022 | Volume
: 9
| Issue : 1 | Page : 1-10 |
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JM-17 Induces G0/G1 Cell cycle arrest in human breast cancer cells through the downregulation of androgen receptors and cyclin-dependent kinase 4 protein expression
Guan-Yi Lai1, Hardy Chan2, Tzu-Chi Chen2, Wen-Jui Lee3, Yuan-Soon Ho4
1 Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan
2 Allianz Pharmascience Limited, Taipei, Taiwan
3 Ph.D. Program for Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University and National Health Research Institutes, Taiwan
4 Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University; Department of Laboratory Medicine, Taipei Medical University Hospital; TMU Research Center of Cancer Translational Medicine, Taipei Medical University; School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan
Correspondence Address:
Dr. Yuan-Soon Ho
School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, No.250 Wu-Hsing Street, Taipei City 110
Taiwan
 Source of Support: None, Conflict of Interest: None
DOI: 10.4103/JCRP.JCRP_11_21
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Background: Locally advanced breast cancer (BC) remains a clinical challenge for patients as many will eventually develop distant metastases despite receiving appropriate therapies. Materials and Methods: In this study, we have analyzed the expression of androgen receptors (AR) in a series of BC cell lines and found their expressions rather ubiquitous across many different cell lines. Moreover, we have demonstrated that JM-17 [(1E,4Z,6E)-4-(cyclobutylmethyl)-1,7-bis (3,4-dimethoxyphenyl)-5-hydroxyhepta-1,4,6-trien-3-one], a synthetic curcumin derivative, exhibited suitable antitumor activities on most of the BC cell lines tested. Results: Human MDA-MB-231 cells were treated with JM-17, and the results demonstrated that JM-17-induced cell cycle proliferation arrested at the G0/G1 phase in a dose-dependent manner. Cell cycle-regulated proteins, such as cyclin-dependent kinases 4 (CDK4), were downregulated and p21 was upregulated. We further demonstrated that JM-17 treatment reduced AR expressions in MDA-MB-231 cells. The AR/CDK4 protein complex was demonstrated for the first time using a fluorescence resonance energy transfer (FRET) activity assay and immunohistochemistry (IHC) staining. JM-17 reduced the FRET activity in vitro. An in vivo study further demonstrated that JM-17 (20 mg/kg) decreased considerably MDA-MB-231 xenograft tumor growth. Conclusion: AR-mediated BC formation is a factor that clinicians often neglect. Our study demonstrated that JM-17 could be a promising agent against specific targets in AR-positive BC patients.
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