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

Wen-Ling Cheng; Ting-Yu Lin; Yen-Hsueh Tseng; Fang-Hua Chu; Pin-Ju Chueh; Yueh-Hsiung Kuo; Sheng-Yang Wang

doi:10.1055/s-0030-1250177

Planta Medica, Table of Contents

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

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 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 D₃, and upregulation of p21^WAF‐1/Cip1 by a p53-independent mechanism.

Key words

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

Full Text

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Sheng-Yang Wang

Department of Forestry
National Chung-Hsing University

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