title: Tanshinone I suppresses growth and invasion of human breast cancer cells, MDA-MB-231, through regulation of adhesion molecules.
abstract: The role of cell adhesion molecules has been studied extensively in the process of inflammation, and these molecules are critical components of carcinogenesis and cancer metastasis. This study investigated the effect of tanshinone I derived from the traditional herbal medicine, Salvia miltiorrhiza Bunge, on the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in tumor necrosis factor-alpha (TNF-alpha)-stimulated endothelial cells. Furthermore, this study investigated the effect of tanshinone I on cancer growth, invasion and angiogenesis on human breast cancer cells MDA-MB-231, both in vitro and in vivo. Tanshinone I dose dependently inhibited ICAM-1 and VCAM-1 expressions in human umbilical vein endothelial cells (HUVECs) that were stimulated with TNF-alpha for 6 h. Pretreatment with tanshinone I significantly reduced adhesion of either monocyte U937 or MDA-MB-231 cells to HUVECs. Interestingly, the inhibitory effect of tanshinone I on monocyte and cancer cell adhesion to HUVECs was mimicked by transfection with ICAM-1 and VCAM-1 small interfering RNA. In addition, tanshinone I effectively inhibited TNF-alpha-induced production of vascular endothelial growth factor (VEGF) and VEGF-mediated tube formation in HUVECs. Tanshinone I also inhibited TNF-alpha-induced VEGF production in MDA-MB-231 cells and migration of MDA-MB-231 cells through extracellular matrix. Additionally, reduction of tumor mass volume and decrease of metastasis incidents by tanshinone I were observed in vivo. In conclusion, this study provides a potential mechanism for the anticancer effect of tanshinone I on breast cancer cells, suggesting that tanshinone I may serve as an effective drug for the treatment of breast cancer.
authors.affiliation: Department of Pharmacology, School of Medicine, Institute of Health Sciences, Gyeongsang National University, 92 Chilam-dong, Jinju, South Korea.
authors.forename: Irina Tsoy
authors.initials: IT
authors.lastname: Nizamutdinova
authors.forename: Gyeong Won
authors.initials: GW
authors.lastname: Lee
authors.forename: Jong Sil
authors.initials: JS
authors.lastname: Lee
authors.forename: Min Kyung
authors.initials: MK
authors.lastname: Cho
authors.forename: Kun Ho
authors.initials: KH
authors.lastname: Son
authors.forename: Su Jin
authors.initials: SJ
authors.lastname: Jeon
authors.forename: Sam Sik
authors.initials: SS
authors.lastname: Kang
authors.forename: Yeong Shik
authors.initials: YS
authors.lastname: Kim
authors.forename: Jae Heun
authors.initials: JH
authors.lastname: Lee
authors.forename: Han Geuk
authors.initials: HG
authors.lastname: Seo
authors.forename: Ki Churl
authors.initials: KC
authors.lastname: Chang
authors.forename: Hye Jung
authors.initials: HJ
authors.lastname: Kim
mesh_terms: D045784:Abietanes; D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects; D002450:Cell Communication; D049109:Cell Proliferation / Q000187:drug effects; D042783:Endothelial Cells / Q000166:cytology; D005260:Female; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis / Q000502:physiology*; D051379:Mice; D009361:Neoplasm Invasiveness; D010616:Phenanthrenes / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis / Q000502:physiology*
chemical_list: D045784:Abietanes; D020533:Angiogenesis Inhibitors; D000972:Antineoplastic Agents, Phytogenic; D010616:Phenanthrenes; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; C021751:tanshinone; D018799:Intercellular Adhesion Molecule-1