Tanshinone I suppresses growth and invasion of human breast cancer cells, MDA-MB-231, through regulation of adhesion molecules.
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.
Nizamutdinova
Irina Tsoy
IT
Department of Pharmacology, School of Medicine, Institute of Health Sciences, Gyeongsang National University, 92 Chilam-dong, Jinju, South Korea.
Lee
Gyeong Won
GW
Lee
Jong Sil
JS
Cho
Min Kyung
MK
Son
Kun Ho
KH
Jeon
Su Jin
SJ
Kang
Sam Sik
SS
Kim
Yeong Shik
YS
Lee
Jae Heun
JH
Seo
Han Geuk
HG
Chang
Ki Churl
KC
Kim
Hye Jung
HJ
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*
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