G-1 Inhibits breast cancer cell growth via targeting colchicine-binding site of tubulin to interfere with microtubule assembly

Xiangmin Lv, Chunbo He, Cong Huang, Guohua Hua, Zhengfeng Wang, Steven W. Remmenga, Kerry J. Rodabough, Adam R. Karpf, Jixin Dong, John S. Davis, Cheng Wang

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

G-protein-coupled estrogen receptor 1 (GPER1) has been reported to play a significant role in mediating the rapid estrogen actions in a wide range of normal and cancer cells. G-1 was initially developed as a selective agonist for GPER. However, the molecular mechanisms underlying the actions of G-1 are unknown, and recent studies report inconsistent effects of G-1 on the growth of breast cancer cells. By employing highresolution laser scanning confocal microscopy and time-lapse imaging technology, as well as biochemical analyses, in the current study, we provide convincing in vitro and in vivo evidence that G-1 is able to suppress the growth of breast cancer cells independent of the expression status of GPERs and classic estrogen receptors. Interestingly, we found that triple-negative breast cancer cells (TNBC) are very sensitive to G-1 treatment. We found that G-1 arrested the cell cycle in the prophase of mitosis, leading to caspase activation and apoptosis of breast cancer cells. Our mechanistic studies indicated that G-1, similar to colchicine and 2-methoxyestradiol, binds to colchicine binding site on tubulin, inhibiting tubulin polymerization and subsequent assembly of normal mitotic spindle apparatus during breast cancer cell mitosis. Therefore, G-1 is a novel microtubule-Targeting agent and could be a promising antimicrotubule drug for breast cancer treatment, especially for TNBC treatment.

Original languageEnglish (US)
Pages (from-to)1080-1091
Number of pages12
JournalMolecular cancer therapeutics
Volume16
Issue number6
DOIs
StatePublished - Jun 2017

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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