Chintharlapalli Sudhakar, Papineni Sabitha, Abdelrahim Maen, Abudayyeh Ala, Jutooru Indira, Chadalapaka Gayathri, Wu Fei, Mertens-Talcott Susanne, Vanderlaag Kathy, Cho Sung Dae, Smith Roger, Safe Stephen
Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, TX 77843-4466, USA.
Int J Cancer. 2009 Oct 15;125(8):1965-74. doi: 10.1002/ijc.24530.
Methyl 2-cyano-3,11-dioxo-18beta-olean-1,12-dien-30-oate (CDODA-Me) is a synthetic derivative of glycyrrhetinic acid, a triterpenoid phytochemical found in licorice extracts. CDODA-Me inhibited growth of RKO and SW480 colon cancer cells and this was accompanied by decreased expression of Sp1, Sp3 and Sp4 protein and mRNA and several Sp-dependent genes including survivin, vascular endothelial growth factor (VEGF), and VEGF receptor 1 (VEGFR1 or Flt-1). CDODA-Me also induced apoptosis, arrested RKO and SW480 cells at G(2)/M, and inhibited tumor growth in athymic nude mice bearing RKO cells as xenografts. CDODA-Me decreased expression of microRNA-27a (miR-27a), and this was accompanied by increased expression of 2 miR-27a-regulated mRNAs, namely ZBTB10 (an Sp repressor) and Myt-1 which catalyzes phosphorylation of cdc2 to inhibit progression of cells through G(2)/M. Both CDODA-Me and antisense miR-27a induced comparable responses in RKO and SW480 cells, suggesting that the potent anticarcinogenic activity of CDODA-Me is due to repression of oncogenic miR-27a.
2-氰基-3,11-二氧代-18β-齐墩果-1,12-二烯-30-酸甲酯（CDODA-Me）是甘草次酸的一种合成衍生物，甘草次酸是一种存在于甘草提取物中的三萜类植物化学物质。CDODA-Me抑制RKO和SW480结肠癌细胞的生长，同时伴随着Sp1、Sp3和Sp4蛋白及mRNA表达的降低，以及包括生存素、血管内皮生长因子（VEGF）和VEGF受体1（VEGFR1或Flt-1）在内的几种Sp依赖性基因表达的降低。CDODA-Me还诱导细胞凋亡，使RKO和SW480细胞停滞于G(2)/M期，并抑制携带RKO细胞异种移植物的无胸腺裸鼠的肿瘤生长。CDODA-Me降低了微小RNA-27a（miR-27a）的表达，同时伴随着2种miR-27a调控的mRNA表达的增加，即ZBTB10（一种Sp阻遏物）和催化cdc2磷酸化以抑制细胞通过G(2)/M期进程的Myt-1。CDODA-Me和反义miR-27a在RKO和SW480细胞中诱导了类似的反应，表明CDODA-Me强大的抗癌活性归因于致癌性miR-27a的抑制。
