Carcinogenesis Advance Access published online on June 26, 2008
Carcinogenesis, doi:10.1093/carcin/bgn151
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Tanshinone I suppresses growth and invasion of human breast cancer cells, MDA-MB-231, through regulation of adhesion molecules
1 Department of Pharmacology, School of Medicine, Institute of Health Sciences, Gyeongsang National University, Jinju, Korea
2 Department of Internal Medicine, College of Medicine, Gyeongnam Regional Cancer Center, Gyeongsang National University
3 Department of Pathology, College of Medicine, Gyeongsang National University, Jinju, South Korea
4 Department of Pharmacology, College of Oriental Medicine, Dongguk University, Kyungju, Korea
5 Department of Food Science and Nutrition, Andong National University, Andong, Korea
6 Natural Product Research Institute, Seoul National University, Seoul, Korea
* To whom correspondence should be addressed: Hye Jung Kim, Department of Pharmacology, College of Medicine, Gyeongsang National University, 92 Chilam-dong, Jinju, South Korea. Tel: +82-55-751-8774; Fax: +82-55-759-0609; E-mail: hyejungkim{at}gnu.ac.kr
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 TNF-
-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- 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 siRNA. In addition, tanshinone I effectively inhibited TNF--induced production of VEGF and VEGF-mediated tube formation in HUVECs. Tanshinone I also inhibited TNF--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 anti-cancer effect of tanshinone I on breast cancer cells, suggesting that tanshinone I may serve as an effective drug for the treatment of breast cancer.
Key Words: breast cancer • ICAM-1 • metastasis • tanshinone I • VCAM-1
The authors are equally contributed Received April 3, 2008; revised June 9, 2008; accepted June 13, 2008.