Oncogenic microRNA-27a is a target for anticancer agent methyl 2-cyano-3,11-dioxo-18beta-olean-1,12-dien-30-oate in colon cancer cells.

Oncogenic microRNA-27a is a target for anticancer agent methyl 2-cyano-3,11-dioxo-18beta-olean-1,12-dien-30-oate in colon cancer cells.
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DOI:
10.1002/ijc.24530
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发表时间:
2009-10-15
影响因子:
6.4
通讯作者:
Safe, Stephen
Safe, Stephen
中科院分区:
医学1区
文献类型:
--
作者:
Chintharlapalli, Sudhakar;Papineni, Sabitha;Abdelrahim, Maen;Abudayyeh, Ala;Jutooru, Indira;Chadalapaka, Gayathri;Wu, Fei;Mertens-Talcott, Susanne;Vanderlaag, Kathy;Cho, Sung Dae;Smith, Roger, III;Safe, Stephen

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甲基2-氰基-3,11-二氧基-18β-齐olean-1,12-二烯-30-oate (CDODA-Me)是甘草次酸的合成衍生物,甘草次酸是一种在甘草提取物中发现的三萜植物化学物质。CDODA-Me抑制RKO和SW480结肠癌细胞的生长,并伴有Sp1、Sp3和Sp4蛋白、mRNA和几种sp依赖基因(包括survivin、血管内皮生长因子(VEGF)和VEGF受体1 (VEGFR1或Flt-1)的表达降低。在移植RKO细胞的胸腺裸鼠中,CDODA-Me还能诱导细胞凋亡,在G2/M浓度下抑制RKO和SW480细胞,抑制肿瘤生长。CDODA-Me降低了microRNA-27a (miR-27a)的表达,并伴有两种miR-27a调节mrna的表达增加,即ZBTB10(一种Sp抑制因子)和Myt-1,后者催化cdc2的磷酸化,通过G2/M抑制细胞的进展。CDODA-Me和反义miR-27a在RKO和SW480细胞中诱导的反应相似,这表明CDODA-Me的强效抗癌活性是由于抑制致癌的miR-27a。
Methyl 2-cyano-3,11-dioxo-18β-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 G2/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 two miR-27a-regulated mRNAs, namely ZBTB10 (an Sp repressor) and Myt-1 which catalyzes phosphorylation of cdc2 to inhibit progression of cells through G2/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.
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