Inhibitory effect of human breast cancer cell proliferation via p21-mediated G1 cell cycle arrest by araliadiol isolated from aralia cordata thunb.
Journal
Planta Medica
Journal Volume
77
Journal Issue
2
Pages
164-168
Date Issued
2011
Author(s)
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 g/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 M. 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 p21WAF1/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 p21WAF1/Cip1 by a p53-independent mechanism. ? Georg Thieme Verlag KG Stuttgart New York.
Subjects
Aralia cordata; Araliaceae; araliadiol; cell cycle; cytotoxicity; G1 arrest
SDGs
Other Subjects
antineoplastic agent; beta actin; checkpoint kinase 2; cyclin D1; cyclin D3; cyclin dependent kinase 2; cyclin dependent kinase 4; cyclin dependent kinase 6; cyclin E; pentadeca 1 diene 4,6 diyne 3,8 diol; plumbagin; polyacetylene derivative; protein p16; protein p21; protein p27; protein p53; retinoblastoma protein; unclassified drug; antineoplastic activity; Aralia cordata; article; breast adenocarcinoma; cancer cell; cancer cell culture; cancer inhibition; cell cycle arrest; cell cycle G1 phase; cell cycle S phase; cell strain MCF 7; chemical structure; controlled study; cytotoxicity; dose response; down regulation; human; human cell; IC 50; infrared spectroscopy; mass spectrometry; medicinal plant; nuclear magnetic resonance; phase transition; plant leaf; protein expression; protein phosphorylation; ultraviolet spectroscopy; upregulation; Adenocarcinoma; Aralia; Breast Neoplasms; Cell Cycle; Cell Cycle Proteins; Cell Line, Tumor; Cell Proliferation; Cyclin-Dependent Kinase Inhibitor p21; Dose-Response Relationship, Drug; Female; G1 Phase; Growth Inhibitors; Humans; Plant Leaves; Polyacetylenes; S Phase; Aralia cordata; Araliaceae
Type
journal article