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Fangchinoline induces G1 arrest in breast cancer cells through cell-cycle regulation.

Abstract
Fangchinoline, an alkaloid derived from the dry roots of Stephaniae tetrandrine S. Moore (Menispermaceae), has been shown to possess cytotoxic, anti-inflammatory, and antioxidant properties. In this study, we used Fangchinoline to inhibit breast cancer cell proliferation and to investigate its underlying molecular mechanisms. Human breast cancer cell lines, MCF-7 and MDA-MB-231, were both used in this study. We found that Fangchinoline significantly decreased cell proliferation in a dose-dependent manner and induced G1-phase arrest in both cell lines. In addition, upon analysis of expression of cell cycle-related proteins, we found that Fangchinoline reduced expression of cyclin D1, cyclin D3, and cyclin E, and increased expression of the cyclin-dependent kinase (CDK) inhibitors, p21/WAF1, and p27/KIP1. Moreover, Fangchinoline also inhibited the kinase activities of CDK2, CDK4, and CDK6. These results suggest that Fangchinoline can inhibit human breast cancer cell proliferation and thus may have potential applications in cancer therapy.
AuthorsZhibo Xing, Youxue Zhang, Xianyu Zhang, Yanmei Yang, Yuyan Ma, Da Pang
JournalPhytotherapy research : PTR (Phytother Res) Vol. 27 Issue 12 Pg. 1790-4 (Dec 2013) ISSN: 1099-1573 [Electronic] England
PMID23401195 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2013 John Wiley & Sons, Ltd.
Chemical References
  • Antineoplastic Agents, Phytogenic
  • Benzylisoquinolines
  • CCND1 protein, human
  • CCND3 protein, human
  • CCNE1 protein, human
  • CDKN1A protein, human
  • Cyclin D3
  • Cyclin E
  • Cyclin-Dependent Kinase Inhibitor p21
  • Drugs, Chinese Herbal
  • Oncogene Proteins
  • Cyclin D1
  • Cyclin-Dependent Kinase Inhibitor p27
  • fangchinoline
  • CDK2 protein, human
  • CDK4 protein, human
  • CDK6 protein, human
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinase 6
Topics
  • Antineoplastic Agents, Phytogenic (pharmacology)
  • Benzylisoquinolines (pharmacology)
  • Breast Neoplasms (metabolism, pathology)
  • Cell Cycle Checkpoints (drug effects)
  • Cell Line, Tumor
  • Cell Proliferation
  • Cyclin D1 (metabolism)
  • Cyclin D3 (metabolism)
  • Cyclin E (metabolism)
  • Cyclin-Dependent Kinase 2 (metabolism)
  • Cyclin-Dependent Kinase 4 (metabolism)
  • Cyclin-Dependent Kinase 6 (metabolism)
  • Cyclin-Dependent Kinase Inhibitor p21 (metabolism)
  • Cyclin-Dependent Kinase Inhibitor p27 (metabolism)
  • Dose-Response Relationship, Drug
  • Drugs, Chinese Herbal (pharmacology)
  • Female
  • G1 Phase (drug effects)
  • Humans
  • Oncogene Proteins (metabolism)

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