Research article summary (published 13 Oct 2009):

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.

Full 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.

Author information

Author/s: Chintharlapalli, Sudhakar (S); Papineni, Sabitha (S); Abdelrahim, Maen (M); Abudayyeh, Ala (A); Jutooru, Indira (I); Chadalapaka, Gayathri (G); Wu, Fei (F); Mertens-Talcott, Susanne (S); Vanderlaag, Kathy (K); Cho, Sung Dae (SD); Smith, Roger (R); Safe, Stephen (S);

Affiliation: Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, TX 77843-4466, USA.

Grants: R01CA108718 (Agency:NCI NIH HHS) ; R01CA112337 (Agency:NCI NIH HHS) ; R01CA135571 (Agency:NCI NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

Journal: International journal of cancer. Journal international du cancer (Int J Cancer), published in United States. (Language: eng)

Reference: 2009-Oct; vol 125 (issue 8) : pp 1965-74

Dates: Created 2009/08/26; Completed 2009/09/21; Revised 2009/10/26;

PMID: 19582879, status: MEDLINE (last retrieval date: 10/27/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

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 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

Associated Chemicals: Antineoplastic Agents (0) ; MIRN27 microRNA, human (0) ; MicroRNAs (0) ; PPAR gamma (0) ; RNA, Messenger (0) ; RNA, Small Interfering (0) ; Sp Transcription Factors (0) ; methyl 2-cyano-3,11-dioxo-18beta-olean-1,12-dien-30-oate (0) ; Glycyrrhetinic Acid (471-53-4)

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