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Decursin exerts anti-cancer activity in MDA-MB-231 breast cancer cells via inhibition of the Pin1 activity and enhancement of the Pin1/p53 association

Phytother Res. 2014 Feb;28(2):238-44. doi: 10.1002/ptr.4986. Epub 2013 Apr 12.

Abstract

The peptidyl-prolyl cis/trans isomerase Pin1 is overexpressed in a wide variety of cancer cells and thus considered as an important target molecule for cancer therapy. This study demonstrates that decursin, a bioactive compound from Angelica gigas, exert the anti-cancer effect against breast cancer cells via regulation of Pin1 and its related signaling molecules. We observed that decursin induced G1 arrest with decrease in cyclin D1 level in Pin1-expressing breast cancer cells MDA-MB-231, but not Pin1-non-expressing breast cancer cells MDA-MB-157. In addition, decursin significantly reduced protein expression and enzymatic activity of Pin1 in MDA-MB-231 cells. Further, we found that decursin treatment enhanced the p53 expression level and failed to down-regulate Pin1 in the cells transfected with p53 siRNA, indicating the importance of p53 in the decursin-mediated Pin1 inhibition in MDA-MB-231 cells. Decursin stimulated association between Pin1 to p53. Moreover, decursin facilitated p53 transcription in MDA-MB-231 cells. Overall, our current study suggests the potential of decursin as an attractive cancer therapeutic agent for breast cancer by targeting Pin1 protein.

Keywords: Pin1; anti-cancer; breast cancer; cell cycle; decursin; p53.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angelica / chemistry
  • Benzopyrans / pharmacology*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Butyrates / pharmacology*
  • Cell Cycle Checkpoints
  • Cell Line, Tumor
  • Cyclin D1 / metabolism
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • NIMA-Interacting Peptidylprolyl Isomerase
  • Peptidylprolyl Isomerase / genetics
  • Peptidylprolyl Isomerase / metabolism*
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Benzopyrans
  • Butyrates
  • CCND1 protein, human
  • NIMA-Interacting Peptidylprolyl Isomerase
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Cyclin D1
  • decursin
  • PIN1 protein, human
  • Peptidylprolyl Isomerase