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.

Abstract

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.

• Authors: Sudhakar Chintharlapalli, Sabitha Papineni, Maen Abdelrahim, Ala Abudayyeh, Indira Jutooru, Gayathri Chadalapaka, Fei Wu, Susanne Mertens-Talcott, Kathy Vanderlaag, Sung Dae Cho, Roger Smith 3rd, Stephen Safe
• Journal: International journal of cancer (Int J Cancer) Vol. 125 Issue 8 Pg. 1965-74 (Oct 15 2009) ISSN: 1097-0215 [Electronic] United States
• PMID: 19582879 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• MIRN27 microRNA, human
• MicroRNAs
• PPAR gamma
• RNA, Messenger
• RNA, Small Interfering
• Sp Transcription Factors
• methyl 2-cyano-3,11-dioxo-18beta-olean-1,12-dien-30-oate
• Glycyrrhetinic Acid

Topics

• Animals
• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Blotting, Northern
• Blotting, Western
• Cell Cycle
• Cell Proliferation (drug effects)
• Colonic Neoplasms (drug therapy, genetics, pathology)
• Gene Expression Regulation, Neoplastic (drug effects)
• Glycyrrhetinic Acid (analogs & derivatives, chemical synthesis, chemistry, pharmacology)
• Humans
• Mice
• Mice, Nude
• MicroRNAs (genetics, metabolism)
• Oncogenes
• PPAR gamma (agonists, metabolism)
• RNA, Messenger (genetics, metabolism)
• RNA, Small Interfering (pharmacology)
• Reverse Transcriptase Polymerase Chain Reaction
• Sp Transcription Factors (antagonists & inhibitors, genetics, metabolism)
• Tumor Cells, Cultured
• Xenograft Model Antitumor Assays