Indole-3-carbinol inhibits tumorigenicity of hepatocellular carcinoma cells via suppression of microRNA-21 and upregulation of phosphatase and tensin homolog

Xinmei Wang, Hongyan He, Yuanzhi Lu, Wei Ren, Kun yu Teng, Chi ling Chiang, Zhaogang Yang, Bo Yu, Shuhao Hsu, Samson T. Jacob, Kalpana Ghoshal, L. James Lee

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

A major obstacle to successful treatment of hepatocellular carcinoma (HCC) is its high resistance to cytotoxic chemotherapy due to overexpression of multidrug resistance genes. Activation of the AKT pathway is known to be involved in chemoresistance in HCC; however, the underlying mechanisms modulating the AKT pathway by chemopreventive agents remain unclear. In the present study, we found that indole-3-carbinol (I3C) treatment for tumor cells repressed the AKT pathway by increasing the expression of phosphatase and tensin homolog (PTEN) in HCC xenograft tumor and HCC cell lines. qRT-PCR data showed that the expression of miR-21 and miR-221&222 was significantly reduced by I3C in HCC cells in vitro and in vivo. Reactivation of the AKT pathway via restoration of miR-21 was reversed by I3C. Ectopic expression of miR-21 mediated-accelerated wound healing was abrogated by I3C. Moreover, reducing the expression of miR-21 by anti-miR decreased the resistance of HCC cells to I3C. These results provide experimental evidences that I3C could function as a miR-21 regulator, leading to repression of the PTEN/AKT pathway and opening a new avenue for eradication of drug-resistant cells, thus potentially helping to improve the therapeutic outcome in patients diagnosed with HCC.

Original languageEnglish (US)
Pages (from-to)244-253
Number of pages10
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1853
Issue number1
DOIs
StatePublished - Jan 1 2015

Keywords

  • Hepatocellular carcinoma
  • Indole-3-carbinol
  • MiR-21
  • MiR-221&222
  • PTEN

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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