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Planta Med 2011; 77(2): 164-168
DOI: 10.1055/s-0030-1250177
Natural Product Chemistry
Original Papers
© Georg Thieme Verlag KG Stuttgart · New York

Inhibitory Effect of Human Breast Cancer Cell Proliferation via p21-Mediated G1 Cell Cycle Arrest by Araliadiol Isolated from Aralia cordata Thunb.

Wen-Ling Cheng1 , Ting-Yu Lin1 , Yen-Hsueh Tseng1 , Fang-Hua Chu2 , Pin-Ju Chueh3 , Yueh-Hsiung Kuo4 , 5 , Sheng-Yang Wang1 , 5
  • 1Department of Forestry, National Chung-Hsing University, Taichung, Taiwan
  • 2School of Forestry and Resource Conservation, National Taiwan University, Taipei, Taiwan
  • 3Institute of Biomedical Science, National Chung-Hsing University, Taichung, Taiwan
  • 4Graduate Institute of Chinese Pharmaceutical Science, China Medical University, Taichung, Taiwan
  • 5Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan
Further Information

Publication History

received March 19, 2010 revised June 28, 2010

accepted July 1, 2010

Publication Date:
17 August 2010 (online)

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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 IC50 value for cytotoxicity of 6.41 µg/mL. Cell cycle analysis revealed that the proportion of cells in the G1 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 G1-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 D3 and cyclin-dependent kinase 4 (cdk4) and an increase in the expression of p21WAF‐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 D3, and upregulation of p21WAF‐1/Cip1 by a p53-independent mechanism.

Key words

araliadiol - cytotoxicity - cell cycle - G1 arrest - Aralia cordata - Araliaceae

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Sheng-Yang Wang

Department of Forestry
National Chung-Hsing University

250 Kuo Kuang Road

Taichung 402

Taiwan

Phone: + 886 4 22 84 03 45-138

Fax: + 886 4 22 87 36 28

Email: taiwanfir@dragon.nchu.edu.tw