Resveratrol inhibits invasion and metastasis of colorectal cancer cells via MALAT1 mediated Wnt/β-catenin signal pathway

PLoS One. 2013 Nov 11;8(11):e78700. doi: 10.1371/journal.pone.0078700. eCollection 2013.

Abstract

Resveratrol, extracted from Chinese herbal medicine Polygonum cuspidatum, is known to inhibit invasion and metastasis of human colorectal cancer (CRC), in which long non-coding Metastasis Associated Lung Adenocarcinoma Transcript 1 (RNA-MALAT1) also plays an important role. Using MALAT1 lentiviral shRNA and over-expression constructs in CRC derived cell lines, LoVo and HCT116, we demonstrated that the anti-tumor effects of resveratrol on CRC are through inhibiting Wnt/β-catenin signaling, thus the expression of its target genes such as c-Myc, MMP-7, as well as the expression of MALAT1. In detail, resveratrol down-regulates MALAT1, resulting in decreased nuclear localization of β-catenin thus attenuated Wnt/β-catenin signaling, which leads to the inhibition of CRC invasion and metastasis. This finding of ours surely provides important pre-clinical evidence supporting future use of resveratrol in prevention and treatment of CRC.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Cell Line, Tumor
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism
  • Cell Nucleus / pathology
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology*
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Male
  • Matrix Metalloproteinase 7 / biosynthesis
  • Matrix Metalloproteinase 7 / genetics
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Proto-Oncogene Proteins c-myc / biosynthesis
  • Proto-Oncogene Proteins c-myc / genetics
  • RNA, Long Noncoding / biosynthesis*
  • RNA, Long Noncoding / genetics
  • RNA, Neoplasm / biosynthesis*
  • RNA, Neoplasm / genetics
  • Resveratrol
  • Stilbenes / pharmacology*
  • Wnt Signaling Pathway / drug effects*
  • Wnt Signaling Pathway / genetics
  • beta Catenin / genetics
  • beta Catenin / metabolism

Substances

  • Antineoplastic Agents, Phytogenic
  • MALAT1 long non-coding RNA, human
  • MYC protein, human
  • Proto-Oncogene Proteins c-myc
  • RNA, Long Noncoding
  • RNA, Neoplasm
  • Stilbenes
  • beta Catenin
  • MMP7 protein, human
  • Matrix Metalloproteinase 7
  • Resveratrol

Grant support

This work was supported by National Natural Science Foundation of China (81202812, 81303102, 81303103), Program of Shanghai Municipal Education Commission (2011JW57, 12YZ058), Shanghai Municipal Health Bureau (ZYSNXD-CC-YJXYY-JS20, 2011ZJ030, 20114Y001, 20114037), Shanghai Key Laboratory of Traditional Chinese Clinical Medicine (C10dz2220200). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.