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

Sudhakar Chintharlapalli, Sabitha Papineni, Maen Abdelrahim, Ala Abudayyeh, Indira Jutooru, Gayathri Chadalapaka, Fei Wu, Susanne Mertens-Talcott, Kathy Vanderlaag, Dae Cho Sung, Roger Smith, Stephen Safe

Research output: Contribution to journalArticle

105 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1965-1974
Number of pages10
JournalInternational Journal of Cancer
Volume125
Issue number8
DOIs
StatePublished - Oct 15 2009

Keywords

  • Anticarcinogenicity
  • CDODA-Me
  • Cell cycle
  • Colon cancer
  • miR-27a

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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