TY - JOUR
T1 - Oncogenic microRNA-27a is a target for anticancer agent methyl 2-cyano-3,11-dioxo-18β-olean-1,12-dien-30-oate in colon cancer cells
AU - Chintharlapalli, Sudhakar
AU - Papineni, Sabitha
AU - Abdelrahim, Maen
AU - Abudayyeh, Ala
AU - Jutooru, Indira
AU - Chadalapaka, Gayathri
AU - Wu, Fei
AU - Mertens-Talcott, Susanne
AU - Vanderlaag, Kathy
AU - Sung, Dae Cho
AU - Smith, Roger
AU - Safe, Stephen
PY - 2009/10/15
Y1 - 2009/10/15
N2 - 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 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 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.
AB - 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 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 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.
KW - Anticarcinogenicity
KW - CDODA-Me
KW - Cell cycle
KW - Colon cancer
KW - miR-27a
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U2 - 10.1002/ijc.24530
DO - 10.1002/ijc.24530
M3 - Article
C2 - 19582879
AN - SCOPUS:67650142347
SN - 0020-7136
VL - 125
SP - 1965
EP - 1974
JO - International journal of cancer
JF - International journal of cancer
IS - 8
ER -