3,3'-Diindolylmethane induces anti-human gastric cancer cells by the miR-30e-ATG5 modulating autophagy

Biochem Pharmacol. 2016 Sep 1:115:77-84. doi: 10.1016/j.bcp.2016.06.018. Epub 2016 Jun 29.

Abstract

3,3'-Diindolylmethane (DIM), a class of relatively non-toxic indole derivatives from cruciferous vegetables, has been reported as a promising anticancer phytochemical, but the underlying molecular mechanism is not completely elucidated. In the present study we report a novel regulation of autophagy by DIM in human gastric cancer cells. We found that DIM dose-dependently inhibited the growth of gastric cancer cells in vitro and in vivo. Moreover, ATG5 and LC3 were activated by DIM in gastric cancer cells. Furthermore, miR-30e was down-regulated by DIM and miR-30e targeted the 3'-UTR of ATG5 to inhibit its translation. Overall, these results suggest that DIM may through the miR-30e-ATG5 modulating autophagy inhibit the proliferation of gastric cancer cells.

Keywords: 3,3′-Diindolylmethane; ATG5; Autophagy; Gastric cancer; miR-30e.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Autophagy / drug effects*
  • Autophagy-Related Protein 5 / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Female
  • Humans
  • Indoles / pharmacology*
  • Mice
  • Mice, Nude
  • MicroRNAs / metabolism*
  • Stomach Neoplasms / drug therapy*
  • Xenograft Model Antitumor Assays

Substances

  • ATG5 protein, human
  • Antineoplastic Agents, Phytogenic
  • Autophagy-Related Protein 5
  • Indoles
  • MIRN30b microRNA, human
  • MicroRNAs
  • 3,3'-diindolylmethane