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

8 Citations (Scopus)

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

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Colchicine
Tubulin
Microtubules
Binding Sites
Breast Neoplasms
Growth
Triple Negative Breast Neoplasms
Mitosis
Time-Lapse Imaging
Prophase
Spindle Apparatus
Estrogen Receptor alpha
Caspases
G-Protein-Coupled Receptors
Confocal Microscopy
Polymerization
Estrogen Receptors
Cell Cycle
Estrogens
Reference Values

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

G-1 Inhibits breast cancer cell growth via targeting colchicine-binding site of tubulin to interfere with microtubule assembly. / Lv, Xiangmin; He, Chunbo; Huang, Cong; Hua, Guohua; Wang, Zhengfeng; Remmenga, Steven W; Rodabough, Kerry J.; Karpf, Adam R; Dong, Jixin; Davis, John S; Wang, Cheng.

In: Molecular cancer therapeutics, Vol. 16, No. 6, 06.2017, p. 1080-1091.

Research output: Contribution to journalArticle

Lv, Xiangmin ; He, Chunbo ; Huang, Cong ; Hua, Guohua ; Wang, Zhengfeng ; Remmenga, Steven W ; Rodabough, Kerry J. ; Karpf, Adam R ; Dong, Jixin ; Davis, John S ; Wang, Cheng. / G-1 Inhibits breast cancer cell growth via targeting colchicine-binding site of tubulin to interfere with microtubule assembly. In: Molecular cancer therapeutics. 2017 ; Vol. 16, No. 6. pp. 1080-1091.
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