Curcumol inhibits colorectal cancer proliferation by targeting miR-21 and modulated PTEN/PI3K/Akt pathways

Life Sci. 2019 Mar 15:221:354-361. doi: 10.1016/j.lfs.2019.02.049. Epub 2019 Feb 24.

Abstract

Aims: The purpose of this study was to demonstrate how curcumol affected the expression of miR-21 and whether its effects on miR-21 was associated with the activation of PTEN/PI3K/Akt pathways in CRC cells.

Main methods: MTT and xenograft assay were used to examine how curcumol inhibits colorectal cancer (CRC) cells' growth. Q-PCR and western blot analysis were employed to test the role of miR-21 in the inhibition of curcumol on proliferation and PTEN/PI3K/Akt pathways of CRC cells.

Key findings: We found that curcumol effectively inhibited CRC cells from proliferating via the PTEN/PI3K/Akt pathways and reduced expression of miR-21 both in vitro and in vivo. miR-21 mimics were found to decrease the protein level of PTEN and increase the expression of PI3K, phospho-Akt (p-Akt) and NF-κB, while miR-21 sponge (miR-21-SP) enhanced the expression of PTEN and reduced the activity of PI3K, Akt and NF-κB. Furthermore, miR-21-SP strengthened the role of curcumol in up-regulating PTEN and inhibiting PI3K/Akt pathways, but miR-21 reversed the effect of curcumol on the PTEN/PI3K/Akt pathways.

Significance: Our research demonstrated that curcumol reduced the proliferation of CRC cells through PTEN/PI3K/Akt by targeting miR-21 and miR-21 could be a target molecule of curcumol for CRC treatment.

Keywords: Colorectal cancer; Curcumol; PTEN/PI3K/Akt; Proliferation; miR-21.

MeSH terms

  • Animals
  • Apoptosis
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation / drug effects
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / genetics
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Mice
  • Mice, Nude
  • MicroRNAs / drug effects*
  • MicroRNAs / metabolism
  • PTEN Phosphohydrolase
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • Sesquiterpenes / metabolism*
  • Sesquiterpenes / pharmacology*
  • Signal Transduction
  • Xenograft Model Antitumor Assays

Substances

  • MIRN21 microRNA, human
  • MicroRNAs
  • Sesquiterpenes
  • curcumol
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • PTEN Phosphohydrolase
  • PTEN protein, human