title: Chrysin, Abundant in Morinda citrifolia Fruit Water-EtOAc Extracts, Combined with Apigenin Synergistically Induced Apoptosis and Inhibited Migration in Human Breast and Liver Cancer Cells.
abstract: The composition of Morinda citrifolia (M. citrifolia) was determined using high-performance liquid chromatography (HPLC), and the anticancer effects of M. citrifolia extract evaluated in HepG2, Huh7, and MDA-MB-231 cancer cells. M. citrifolia fruit extracts were obtained by using five different organic solvents, including hexane (Hex), methanol (MeOH), ethyl acetate (EtOAc), chloroform (CHCl3), and ethanol (EtOH). The water-EtOAc extracts from M. citrifolia fruits was found to have the highest anticancer activity. HPLC data revealed the predominance of chrysin in water-EtOAc extracts of M. citrifolia fruit. Furthermore, the combined effects of cotreatment with apigenin and chrysin on liver and breast cancer were investigated. Treatment with apigenin plus chrysin for 72-96 h reduced HepG2 and MDA-MB-231 cell viability and induced apoptosis through down-regulation of S-phase kinase-associated protein-2 (Skp2) and low-density lipoprotein receptor-related protein 6 (LRP6) expression. However, the combination treatment for 36 h synergistically decreased MDA-MB-231 cell motility but not cell viability through down-regulation of MMP2, MMP9, fibronectin, and snail in MDA-MB-231 cells. Additionally, chrysin combined with apigenin also suppressed tumor growth in human MDA-MB-231 breast cancer cells xenograft through down-regulation of ki-67 and Skp2 protein. The experimental results showed that chrysin combined with apigenin can reduce HepG2 and MDA-MB-231 proliferation and cell motility and induce apoptosis. It also offers opportunities for exploring new drug targets, and further investigations are underway in this regard.
authors.affiliation: National Research Institute of Chinese Medicine , Taipei 11221, Taiwan, ROC.
authors.forename: Cheng
authors.initials: C
authors.lastname: Huang
authors.affiliation: Department of Applied Science, National Hsinchu University of Education , Hsinchu 30014, Taiwan, ROC.
authors.forename: Yu-Xuan
authors.initials: YX
authors.lastname: Wei
authors.affiliation: Department of Applied Science, National Hsinchu University of Education , Hsinchu 30014, Taiwan, ROC.
authors.forename: Ma-Ching
authors.initials: MC
authors.lastname: Shen
authors.affiliation: Department of Applied Science, National Hsinchu University of Education , Hsinchu 30014, Taiwan, ROC.
authors.forename: Yu-Hsuan
authors.initials: YH
authors.lastname: Tu
authors.affiliation: Department of Applied Science, National Hsinchu University of Education , Hsinchu 30014, Taiwan, ROC.
authors.forename: Chia-Chi
authors.initials: CC
authors.lastname: Wang
authors.affiliation: Department of Applied Science, National Hsinchu University of Education , Hsinchu 30014, Taiwan, ROC.
authors.forename: Hsiu-Chen
authors.initials: HC
authors.lastname: Huang
mesh_terms: D000818:Animals; D047310:Apigenin / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation; D004357:Drug Synergism; D005260:Female; D005419:Flavonoids / Q000008:administration & dosage* / Q000302:isolation & purification; D005638:Fruit / Q000737:chemistry; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D060488:Low Density Lipoprotein Receptor-Related Protein-6 / Q000235:genetics / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D032066:Morinda / Q000737:chemistry*; D010936:Plant Extracts / Q000008:administration & dosage* / Q000302:isolation & purification; D044786:S-Phase Kinase-Associated Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D005419:Flavonoids; D060488:Low Density Lipoprotein Receptor-Related Protein-6; D010936:Plant Extracts; D044786:S-Phase Kinase-Associated Proteins; C043561:chrysin; D047310:Apigenin; D020778:Matrix Metalloproteinase 2
keywords: apigenin; apoptosis; chrysin; epithelial−mesenchymal transition; xenografts