期刊
FOOD AND CHEMICAL TOXICOLOGY
卷 100, 期 -, 页码 149-160出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.fct.2016.12.032
关键词
Crataegus pinnatifida; MDA-MB-231; Ursolic acid; Apoptosis; Cell cycle; Semi-preparative HPLC
资金
- Guangdong Province Government (China) through the program of Leading Talent of Guangdong Province
- Pearl River S&T Nova Program of Guangzhou [201610010096]
- Guangdong Special Support Program [2015TQ01N670]
- Fundamental Research Funds for the Central Universities [2015ZZ110]
- National Natural Science Foundation of Guangdong Province [2014A030313242]
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation
- Sun Yat-Sen Memorial Hospital, Sun Yat-sen University
The cytotoxicity and antiproliferative effect of phytochemicals presenting in the fruits of Chinese hawthorn (Crataegus pinnatifida) were evaluated. Shanlihong (Crataegus pinnatifida Bge. var. major N.E.Br.) variety possessed significant levels of flavonoids and triterpenoids, and showed potent antiproliferative effect against HepG(2), MCF-7 and MDA-MB- 231 human cancer cells lines. Triterpenoids-enriched fraction (S9) prepared by Semi-preparative HPLC, and its predominant ingredient ursolic acid (UA) demonstrated remarkably antiproliferative activities for all the tested cancer cell lines. DNA flow cytometric analysis showed that S9 fraction and UA significantly induced G1 arrest in MDA-MB-231 cells in a dose dependent manner. Western blotting analysis revealed that S9 fraction and UA significantly induced PCNA, CDK4, and Cyclin D1 downregulation in MDA-MB-231 cells, followed by p21(Waf1/Cip1) up-regulation. Additionally, flow cytometer and DNA ladder assays indicated that S9 fraction and UA significantly induced MDA-MB-231 cells apoptosis. Mitochondrial death pathway was involved in this apoptosis as significantly induced caspase-9 and caspase-3 activation. These results suggested that triterpenoids-enriched fraction and UA exhibited antiproliferative activity through the cell cycle arrest and apoptosis induction, and was majorly responsible for the potent anticancer activity of Chinese hawthorn. (C) 2016 Elsevier Ltd. All rights reserved.
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