Inhibitory effect of human breast cancer cell proliferation via p21-mediated G1 cell cycle arrest by araliadiol isolated from Aralia cordata Thunb

Planta Med. 2011 Jan;77(2):164-8. doi: 10.1055/s-0030-1250177. Epub 2010 Aug 17.

Abstract

A new polyacetylenic compound, araliadiol, was isolated from the leaves of Aralia cordata Thunb. (Araliaceae). The structure of araliadiol was determined to be 3( S),8( R)-pentadeca-1,9( Z)-diene-4,6-diyne-3,8-diol by MS, NMR, IR, and UV spectroscopic analysis as well as Mosher ester reaction. Araliadiol displayed a significant inhibitory effect on the growth of a human breast adenocarcinoma cell line (MCF-7), with an IC (50) value for cytotoxicity of 6.41 µg/mL. Cell cycle analysis revealed that the proportion of cells in the G (1) phase of the cell cycle increased in a dose-dependent manner (from 54.7 % to 72.0 %) after 48 h exposure to araliadiol at dosages ranging from 0 to 80 µM. The results suggest that araliadiol inhibits cell cycle progression of MCF-7 at the G (1)-S transition. After treatment with araliadiol, phosphorylation of retinoblastoma protein (Rb) in MCF-7 cells was inhibited, accompanied by a decrease in the levels of cyclin D (3) and cyclin-dependent kinase 4 (cdk4) and an increase in the expression of p21 (WAF-1/Cip1). However, the expression of phosphorylated p53 (Ser15) and Chk2 was not altered in MCF-7 cells. These findings indicate that araliadiol exhibits its growth-inhibitory effects on MCF-7 cells through downregulation of cdk4 and cyclin D (3), and upregulation of p21 (WAF-1/Cip1) by a p53-independent mechanism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / pathology
  • Adenocarcinoma / prevention & control
  • Aralia / chemistry*
  • Breast Neoplasms / pathology
  • Breast Neoplasms / prevention & control
  • Cell Cycle / drug effects
  • Cell Cycle Proteins / drug effects
  • Cell Cycle Proteins / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Cyclin-Dependent Kinase Inhibitor p21 / drug effects*
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Dose-Response Relationship, Drug
  • Female
  • G1 Phase / drug effects
  • Growth Inhibitors / pharmacology*
  • Humans
  • Plant Leaves / chemistry
  • Polyynes / chemistry
  • Polyynes / isolation & purification
  • Polyynes / pharmacology*
  • S Phase / drug effects

Substances

  • 3(S),8(R)-pentadeca-1,9(Z)-diene-4,6-diyne-3,8-diol
  • Cell Cycle Proteins
  • Cyclin-Dependent Kinase Inhibitor p21
  • Growth Inhibitors
  • Polyynes