Major triterpenoids in Chinese hawthorn "Crataegus pinnatifida" and their effects on cell proliferation and apoptosis induction in MDA-MB-231 cancer cells. (February 2017)

• Record Type: Journal Article
• Authors: Wen, Lingrong; Guo, Ruixue; You, Lijun; Abbasi, Arshad Mehmood; Li, Tong; Fu, Xiong; Liu, Rui Hai
• Is Part Of: Food and chemical toxicology. Volume 100(2017)
• Page Start: 149
• Page End: 160
• Publication Date: 2017-02
• Subjects: Crataegus pinnatifida -- MDA-MB-231 -- Ursolic acid -- Apoptosis -- Cell cycle -- Semi-preparative HPLC; CC50 half maximal cytotoxicity concentration -- EC50 half maximal effect concentration -- UA ursolic acid -- CA corosolic acid -- OA oleanolic acid -- MA maslinic acid -- CDK4 cyclin-dependent kinase 4 -- PCNA proliferating cell nuclear antigen; Ursolic acid (PubChem CID: 64945) -- Corosolic acid (PubChem CID: 6918774) -- Oleanolic acid (PubChem CID: 10494) -- Maslinic acid (PubChem CID: 73659) -- Epicatechin (PubChem CID: 72276) -- Procyanidine B2 (PubChem CID: 122738); Toxicology -- Periodicals; Food poisoning -- Periodicals; Food Poisoning -- Periodicals; Toxicology -- Periodicals; Toxicologie -- Périodiques; Intoxications alimentaires -- Périodiques; Food poisoning; Toxicology; Periodicals; Electronic journals; 615.9
• DOI: 10.1016/j.fct.2016.12.032
• Languages: English
• ISSNs: 0278-6915

Abstract

Abstract: 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 HepG2, 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. Graphical abstract: Triterpenoids-enriched fraction (S9) was prepared by semi-preparative HPLC. S9 fraction and its predominant ingredient ursolic acid (UA) demonstrated remarkably antiproliferative activities through the cell cycle arrest and apoptosis induction, and was partially responsible for the potent anticancer activity of Chinese hawthorn. Highlights: Shanlihong had potent antiproliferative effect against human cancer cells lines. Triterpenoids-enriched fraction (S9) with potent anticancer activity was prepared by semi-preparative HPLC. S9 fraction and ursolic acid induced MDA-MB-231 cells apoptosis through mitochondrial death pathway. S9 fraction and ursolic acid inhibit cell proliferation via PCNA, Cyclin D1 and CDK4 down-regulation and p21 up-regulation. S9 fraction and ursolic acid may responsible for the potent anticancer activity of Chinese hawthorn.