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.
Cell Death Dis. 2013 Oct 17;4(10):e869. doi: 10.1038/cddis.2013.397.
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.
G 蛋白偶联雌激素受体 1（GPER）最近被报道在不同类型的细胞和组织中介导雌激素的非基因组作用。G-1（1-[4-（6-溴苯并[1,3]二恶烷-5-基）-3a,4,5,9b-四氢-3H-环戊[c]喹啉-8-基]-乙酮）被开发为 GPER 的一种有效和选择性激动剂。G-1 已被证明通过激活 GPER 诱导促进癌细胞增殖的基因表达和激活途径。在这里，我们证明 G-1 具有与长春花生物碱（常用的化疗药物）类似的抗癌潜力，其机制类似。我们发现 G-1 可阻止微管聚合，从而中断卵巢癌细胞中的微管组装，导致有丝分裂前期细胞周期停滞，并抑制卵巢癌细胞增殖。G-1 处理还诱导卵巢癌细胞凋亡。G-1 靶向微管抑制卵巢癌细胞增殖的能力使其成为治疗卵巢癌的有前途的候选药物。
