TY - JOUR
T1 - G-1 Inhibits breast cancer cell growth via targeting colchicine-binding site of tubulin to interfere with microtubule assembly
AU - Lv, Xiangmin
AU - He, Chunbo
AU - Huang, Cong
AU - Hua, Guohua
AU - Wang, Zhengfeng
AU - Remmenga, Steven W.
AU - Rodabough, Kerry J.
AU - Karpf, Adam R.
AU - Dong, Jixin
AU - Davis, John S.
AU - Wang, Cheng
N1 - Publisher Copyright:
© 2017 American Association for Cancer Research.
PY - 2017/6
Y1 - 2017/6
N2 - 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.
AB - 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.
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U2 - 10.1158/1535-7163.MCT-16-0626
DO - 10.1158/1535-7163.MCT-16-0626
M3 - Article
C2 - 28258163
AN - SCOPUS:85020932937
SN - 1535-7163
VL - 16
SP - 1080
EP - 1091
JO - Molecular cancer therapeutics
JF - Molecular cancer therapeutics
IS - 6
ER -