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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, andupregulation of p21WAF-1/Cip1 bya p53-independent mechanism. [ABSTRACT FROM AUTHOR]