title: Flavonoids from Citrus unshiu Marc. inhibit cancer cell adhesion to endothelial cells by selective inhibition of VCAM-1.
abstract: Citrus fruits have been used as edible fruit and a component of traditional medicine for various diseases including cancer since ancient times. Herein, we investigated the anticancer activity of flavonoids of Citrus unshiu Marc. (FCM) focusing on anti-metastatic effects. We prepared FCM and performed experiments using MDA-MB-231 human breast cancer cells. FCM inhibited TNF-induced cancer cell adhesion to human umbilical vein endothelial cells (HUVECs) without showing any toxicity. FCM inhibited the expression of VCAM-1, but not of ICAM-1, on MDA-MB-231 cells as well as HUVECs. FCM inhibited protein kinase C (PKC) phosphorylation, but not Akt phosphorylation. FCM also inhibited cancer cell invasion in a dose-dependent manner, but not MMP-9 expression. In conclusion, this study suggested that FCM inhibits TNF-induced cancer cell adhesion to HUVECs by inhibiting VCAM-1 through inhibition of PKC, providing evidence that FCM have anti-metastatic activity by inhibiting adhesion molecules and invasion on human breast cancer cells.
authors.affiliation: Department of Pharmacology, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 660-702, Republic of Korea.
authors.forename: Hana
authors.initials: H
authors.lastname: Jin
authors.forename: Won Sup
authors.initials: WS
authors.lastname: Lee
authors.forename: Jeong Won
authors.initials: JW
authors.lastname: Yun
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Jung
authors.forename: Sang Mi
authors.initials: SM
authors.lastname: Yi
authors.forename: Hye Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Yung Hyun
authors.initials: YH
authors.lastname: Choi
authors.forename: Gonsup
authors.initials: G
authors.lastname: Kim
authors.forename: Jin-Myung
authors.initials: JM
authors.lastname: Jung
authors.forename: Chung Ho
authors.initials: CH
authors.lastname: Ryu
authors.forename: Sung Chul
authors.initials: SC
authors.lastname: Shin
authors.forename: Soon Chan
authors.initials: SC
authors.lastname: Hong
mesh_terms: D001943:Breast Neoplasms; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002957:Citrus / Q000737:chemistry; D042783:Endothelial Cells / Q000187:drug effects*; D005260:Female; D005419:Flavonoids / Q000008:administration & dosage* / Q000737:chemistry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis / Q000188:drug therapy / Q000473:pathology; D010936:Plant Extracts / Q000008:administration & dosage* / Q000737:chemistry; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
chemical_list: D005419:Flavonoids; D010936:Plant Extracts; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1