Tanshinone IIA from Salvia miltiorrhiza BUNGE inhibits human aortic smooth muscle cell migration and MMP-9 activity through AKT signaling pathway.
Smooth muscle cell (SMC) migration plays an important role in normal angiogenesis and is relevant to disease-related vascular remodeling in conditions such as brain arteriovenous malformations, pulmonary hypertension, arteriosclerosis, and restenosis after angioplasty. In this present study, we showed that tanshinone IIA, the major lipid-soluble pharmacological constituent of Salvia miltiorrhiza BUNGE, inhibits human aortic smooth muscle cell (HASMC) migration and MMP-9 activity. Tanshinone IIA significantly inhibited IkappaBalpha phosphorylation and p65 nuclear translocation through inhibition of AKT phosphorylation. Tanshinone IIA inhibited TNF-alpha-induced ERK and c-jun phosphorylation, but not other MAPKs such as JNK and p38. Tanshinone IIA also inhibited NF-kappaB and AP-1 DNA-binding. Moreover, tanshinone IIA inhibited the migration of TNF-alpha-induced HASMCs. Our results provide evidence that tanshinone IIA has multiple effects in the inhibition of HASMC migration and may offer a therapeutic approach to block HASMC migration.
Jin
Un-Ho
UH
Molecular and Cellular Glycobiology Unit, Department of Biological Sciences, Sungkyunkwan University, Jangan-Gu, Suwon City, Kyunggi-Do 440-746, Korea.
Suh
Seok-Jong
SJ
Chang
Hyen Wook
HW
Son
Jong-Keun
JK
Lee
Seung Ho
SH
Son
Kun-Ho
KH
Chang
Young-Chae
YC
Kim
Cheorl-Ho
CH
D045784:Abietanes; D001011:Aorta / Q000166:cytology; D002465:Cell Movement / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000737:chemistry; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D032389:Myocytes, Smooth Muscle / Q000187:drug effects*; D010616:Phenanthrenes / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D027561:Salvia miltiorrhiza; D015398:Signal Transduction
D045784:Abietanes; D004365:Drugs, Chinese Herbal; D061965:Matrix Metalloproteinase Inhibitors; D010616:Phenanthrenes; C021751:tanshinone; D051057:Proto-Oncogene Proteins c-akt; D020780:Matrix Metalloproteinase 9