title: The G-protein-coupled estrogen receptor agonist G-1 suppresses proliferation of ovarian cancer cells by blocking tubulin polymerization.
abstract: The G-protein-coupled estrogen receptor 1 (GPER) has recently been reported to mediate the non-genomic action of estrogen in different types of cells and tissues. G-1 (1-[4-(6-bromobenzo[1,3] dioxol-5yl)-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinolin-8-yl]-ethanone) was developed as a potent and selective agonist for GPER. G-1 has been shown to induce the expression of genes and activate pathways that facilitate cancer cell proliferation by activating GPER. Here we demonstrate that G-1 has an anticancer potential with a mechanism similar to vinca alkaloids, the commonly used chemotherapy drugs. We found that G-1 blocks tubulin polymerization and thereby interrupts microtubule assembly in ovarian cancer cells leading to the arrest of cell cycle in the prophase of mitosis and the suppression of ovarian cancer cell proliferation. G-1 treatment also induces apoptosis of ovarian cancer cells. The ability of G-1 to target microtubules to suppress ovarian cancer cell proliferation makes it a promising candidate drug for treatment of ovarian cancer.
authors.affiliation: 1] Olson Center for Women's Health, University of Nebraska Medical Center, Omaha, NE, USA [2] Departments of Obstetrics and Gynecology, University of Nebraska Medical Center, Omaha, NE, USA [3] Fred and Pamela Buffet Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: C
authors.initials: C
authors.lastname: Wang
authors.forename: X
authors.initials: X
authors.lastname: Lv
authors.forename: C
authors.initials: C
authors.lastname: He
authors.forename: G
authors.initials: G
authors.lastname: Hua
authors.forename: M-Y
authors.initials: MY
authors.lastname: Tsai
authors.forename: J S
authors.initials: JS
authors.lastname: Davis
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003517:Cyclopentanes / Q000494:pharmacology; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology*; D058105:Polymerization / Q000187:drug effects*; D011418:Prophase / Q000187:drug effects; D011804:Quinolines / Q000494:pharmacology; D011960:Receptors, Estrogen / Q000819:agonists* / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000378:metabolism; D008941:Spindle Apparatus / Q000187:drug effects / Q000378:metabolism; D034421:Sus scrofa; D014404:Tubulin / Q000378:metabolism*
chemical_list: C517943:1-(4-(6-bromobenzo(1,3)dioxol-5-yl)-3a,4,5,9b-tetrahydro-3H-cyclopenta(c)quinolin-8-yl)ethanone; D003517:Cyclopentanes; C109584:GPER1 protein, human; D011804:Quinolines; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled; D014404:Tubulin