Wen Lingrong, Guo Ruixue, You Lijun, Abbasi Arshad Mehmood, Li Tong, Fu Xiong, Liu Rui Hai
School of Food Science and Technology, South China University of Technology, Guangzhou 510640, China; Center of Guangdong Food Green Processing and Nutrition Regulation Engineering Technology, South China University of Technology, Guangzhou, Guangdong Province, 510640, China.
School of Food Science and Technology, South China University of Technology, Guangzhou 510640, China; Center of Guangdong Food Green Processing and Nutrition Regulation Engineering Technology, South China University of Technology, Guangzhou, Guangdong Province, 510640, China.
Food Chem Toxicol. 2017 Feb;100:149-160. doi: 10.1016/j.fct.2016.12.032. Epub 2016 Dec 23.
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, 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 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.
对中国山楂（Crataegus pinnatifida）果实中所含植物化学物质的细胞毒性和抗增殖作用进行了评估。山里红（Crataegus pinnatifida Bge. var. major N.E.Br.）品种含有大量黄酮类化合物和三萜类化合物，并对HepG、MCF-7和MDA-MB-231人癌细胞系表现出强大的抗增殖作用。通过半制备高效液相色谱法制备的富含三萜类化合物的组分（S9）及其主要成分熊果酸（UA）对所有测试的癌细胞系均表现出显著的抗增殖活性。DNA流式细胞术分析表明，S9组分和UA以剂量依赖性方式显著诱导MDA-MB-231细胞的G1期阻滞。蛋白质免疫印迹分析显示，S9组分和UA显著诱导MDA-MB-231细胞中PCNA、CDK4和细胞周期蛋白D1的下调，随后p21上调。此外，流式细胞仪和DNA梯状条带分析表明，S9组分和UA显著诱导MDA-MB-231细胞凋亡。线粒体死亡途径参与了这种凋亡，因为显著诱导了caspase-9和caspase-3的激活。这些结果表明，富含三萜类化合物的组分和UA通过细胞周期阻滞和诱导凋亡表现出抗增殖活性，并且主要负责中国山楂强大的抗癌活性。
