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Received: 2009-05-22

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Journal of Zhejiang University SCIENCE B 2009 Vol.10 No.9 P.668~674

10.1631/jzus.B0920149


Ursolic acid inhibits proliferation and induces apoptosis of HT-29 colon cancer cells by inhibiting the EGFR/MAPK pathway


Author(s):  Jian-zhen SHAN, Yan-yan XUAN, Shu ZHENG, Qi DONG, Su-zhan ZHANG

Affiliation(s):  Department of Traditional Chinese Medicine, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China; more

Corresponding email(s):   zhang1873@gmail.com, zrsj@zju.edu.cn

Key Words:  Colon cancer, Ursolic acid, Epidermal growth factor receptor (EGFR), Mitogen-activated protein kinase (MAPK), Apoptosis


Jian-zhen SHAN, Yan-yan XUAN, Shu ZHENG, Qi DONG, Su-zhan ZHANG. Ursolic acid inhibits proliferation and induces apoptosis of HT-29 colon cancer cells by inhibiting the EGFR/MAPK pathway[J]. Journal of Zhejiang University Science B, 2009, 10(9): 668~674.

@article{title="Ursolic acid inhibits proliferation and induces apoptosis of HT-29 colon cancer cells by inhibiting the EGFR/MAPK pathway",
author="Jian-zhen SHAN, Yan-yan XUAN, Shu ZHENG, Qi DONG, Su-zhan ZHANG",
journal="Journal of Zhejiang University Science B",
volume="10",
number="9",
pages="668~674",
year="2009",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B0920149"
}

%0 Journal Article
%T Ursolic acid inhibits proliferation and induces apoptosis of HT-29 colon cancer cells by inhibiting the EGFR/MAPK pathway
%A Jian-zhen SHAN
%A Yan-yan XUAN
%A Shu ZHENG
%A Qi DONG
%A Su-zhan ZHANG
%J Journal of Zhejiang University SCIENCE B
%V 10
%N 9
%P 668~674
%@ 1673-1581
%D 2009
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B0920149

TY - JOUR
T1 - Ursolic acid inhibits proliferation and induces apoptosis of HT-29 colon cancer cells by inhibiting the EGFR/MAPK pathway
A1 - Jian-zhen SHAN
A1 - Yan-yan XUAN
A1 - Shu ZHENG
A1 - Qi DONG
A1 - Su-zhan ZHANG
J0 - Journal of Zhejiang University Science B
VL - 10
IS - 9
SP - 668
EP - 674
%@ 1673-1581
Y1 - 2009
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B0920149


Abstract: 
Objective: To investigate the effects of ursolic acid on the proliferation and apoptosis of human HT-29 colon cancer cells. Methods: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry assays were performed to evaluate the effects of ursolic acid on the growth and apoptosis of HT-29 cells. Western blot analysis was applied to investigate the inhibitory effects of ursolic acid on the phosphorylation of the epidermal growth factor receptor (EGFR), extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (p38 MAPK), and the activity of B cell leukemia-2 (Bcl-2), B cell leukemia-xL (Bcl-xL), caspase-3, and caspase-9. Results: ursolic acid inhibited the growth of HT-29 cells in dose- and time-dependent manners. The median inhibition concentration (IC50) values for 24, 48, and 72 h treatment were 26, 20, and 18 μmol/L, respectively. The apoptotic rates of 10, 20, and 40 μmol/L ursolic acid treatments for 24 h were 5.74%, 14.49%, and 33.05%, and for 48 h were 9%, 21.39%, and 40.49%, respectively. ursolic acid suppressed the phosphorylation of EGFR, ERK1/2, p38 MAPK, and JNK, which is well correlated with its growth inhibitory effect. 10, 20, and 40 μmol/L ursolic acid significantly inhibited the proliferation of EGF-stimulated HT-29 cells (P<0.05). Cell proliferation was most significantly inhibited when treated with 10 and 20 μmol/L ursolic acid combined with 200 nmol/L AG 1478 or 10 μmol/L U0126 (P<0.01). Besides, it also down-regulated the expression of Bcl-2 and Bcl-xL and activated caspase-3 and caspase-9. Conclusion: ursolic acid induces apoptosis in HT-29 cells by suppressing the EGFR/MAPK pathway, suggesting that it may be a potent agent for the treatment of colorectal cancer.

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