Dihydrotanshinone I inhibits angiogenesis both in vitro and in vivo
Weipeng Bian
School of Life Science, East China Normal University, Shanghai 200062, China
National Laboratory for Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiaotong University, Shanghai 200240, China
Search for more papers by this authorCorresponding Author
Fei Chen
National Laboratory for Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiaotong University, Shanghai 200240, China
*Corresponding author: Tel /Fax, 86-21-34206022; E-mail, [email protected]Search for more papers by this authorLing Bai
Institute of Mechanobiology and Medical Engineering, Shanghai Jiaotong University, Shanghai 200240, China
Search for more papers by this authorPing Zhang
National Laboratory for Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiaotong University, Shanghai 200240, China
Search for more papers by this authorWenxin Qin
National Laboratory for Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiaotong University, Shanghai 200240, China
Search for more papers by this authorWeipeng Bian
School of Life Science, East China Normal University, Shanghai 200062, China
National Laboratory for Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiaotong University, Shanghai 200240, China
Search for more papers by this authorCorresponding Author
Fei Chen
National Laboratory for Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiaotong University, Shanghai 200240, China
*Corresponding author: Tel /Fax, 86-21-34206022; E-mail, [email protected]Search for more papers by this authorLing Bai
Institute of Mechanobiology and Medical Engineering, Shanghai Jiaotong University, Shanghai 200240, China
Search for more papers by this authorPing Zhang
National Laboratory for Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiaotong University, Shanghai 200240, China
Search for more papers by this authorWenxin Qin
National Laboratory for Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiaotong University, Shanghai 200240, China
Search for more papers by this authorThis work was supported by the grants from the Foundation of Shanghai Municipal Health Bureau (No. 287), and the National High Technology Research and Development Program of China (No. 2006AA020501)
Abstract
Dihydrotanshinone I (DI), a naturally occurring compound extracted from Salvia miltiorrhiza Bunge, has been reported to have cytotoxicity to a variety of tumor cells. In this study, we investigated its anti-angiogenic capacity in human umbilical vein endothelial cells. DI induced a potent cytotoxicity to human umbilical vein endothelial cells, with an IC50 value of approximately 1.28 μg/ml. At 0.25-1 μg/ml, DI dose-dependently suppressed human umbilical vein endothelial cell migration, invasion, and tube formation detected by wound healing, Transwell invasion and Matrigel tube formation assays, respectively. Moreover, DI showed significant in vivo anti-angiogenic activity in chick embryo chorioallantoic membrane assay. DI induced a 61.1% inhibitory rate of microvessel density at 0.2 μg/egg. Taken together, our results showed that DI could inhibit angio-genesis through suppressing endothelial cell proliferation, migration, invasion and tube formation, indicating that DI has a potential to be developed as a novel anti-angiogenic agent.
References
- 1 Folkman J. Tumor angiogenesis: Therapeutic implications. N Engl J Med 1971, 285: 1182–1186.
- 2 Carmeliet P. Angiogenesis in health and disease. Nat Med 2003, 9: 653–660.
- 3 Griffioen AW, Molema G. Angiogenesis: potentials for pharmacologic intervention in the treatment of cancer, cardiovascular diseases, and chronic inflammation. Pharmacol Rev 2000, 52: 237–268.
- 4 Pugh CW, Ratcliffe PJ. Regulation of angiogenesis by hypoxia: role of the HIF system. Nat Med 2003, 9: 677–684.
- 5 Zhou XD. Recurrence and metastasis of hepatocellular carcinoma: Progress and prospects. Hepatobiliary Pancreat Dis Int 2002, 1: 35–41.
- 6 Masiero L, Figg WD, Kohn EC. New anti-angiogenesis agents: Review of the clinical experience with carboxyamido-triazole (CAI), thalidomide, TNP-470 and interleukin-12. Angiogenesis 1997, 1: 23–35.
- 7 Pandya NM, Dhalla NS, Santani DD. Angiogenesis --- a new target for future therapy. Vascul Pharmacol 2006, 44: 265–274.
- 8 Yasumasa I, Izumi M, Yutaka T. Abietane type diterpenoids from Salvia miltiorrhiza. Phytochem 1989, 28: 3139–3141.
- 9
Zhi HB,
Alfermann AW.
Diterpenoid production in hairy root cultures of Salvia miltiorrhiza.
Phytochem
1993, 32: 699–702.
10.1016/S0031-9422(00)95156-2 Google Scholar
- 10 Mosaddik MA. In vitro cytotoxicity of tanshinones isolated from Salvia miltiorrhiza Bunge against P388 lymphocytic leukemia cells. Phytomedicine 2003, 10: 682–685.
- 11 Choi HS, Kim KM. Tanshinones inhibit mast cell degranulation by interfering with IgE receptor-mediated tyrosine phosphorylation of PLCγ2 and MAPK. Planta Med 2004, 79: 178–180.
- 12 Choi HS, Cho DI, Choi HK, Im SY, Ryu SY, Kim KM. Molecular mechanisms of inhibitory activities of tanshinones on lipopolysac-charide-induced nitric oxide generation in RAW 264.7 cells. Arch Pharm Res 2004, 27: 1233–1237.
- 13 Lee SY, Choi DY, Woo ER. Inhibition of osteoclast differentiation by tanshinones from the root of Salvia miltiorrhiza bunge. Arch Pharm Res 2005, 28: 909–913.
- 14 Kang BY, Chung SW, Kim SH, Ryu SY, Kim TS. Inhibition of interleukin--12 and interferon-gamma production in immune cells by tanshinones from Salvia miltiorrhiza. Immunopharmacology 2000, 49: 355–361.
- 15 Airoldi I, Di Carlo E, Cocco C, Taverniti G, D'Antuono T, Ognio E, Watanabe M et al. Endogenous IL-12 triggers an antiangiogenic program in melanoma cells. Proc Natl Acad Sci USA 2007, 104: 3996–4001.
- 16 Roberts DD, Isenberg JS, Ridnour LA, Wink DA. Nitric oxide and its gatekeeper thrombospondin-1 in tumor angiogenesis. Clin Cancer Res 2007, 13: 795–798.
- 17 Grobmyer SR, Kuo A, Orishimo M, Okada SS, Cines DB, Barnathan ES. Determinants of binding and internalization of tissue-type plasminogen activator by human vascular smooth muscle and endothelial cells. J Biol Chem 1993, 268: 13291–13300.
- 18 He Q, Yang B, Lou YJ, Fang RY. Contragestazol (DL111-IT) inhibits proliferation of human androgen-independent prostate cancer cell line PC3 in vitro and in vivo. Asian J Androl 2005, 7: 389–393.
- 19 Lee MS, Moon EJ, Lee SW, Kim MS, Kim KW, Kim YJ. Angiogenic activity of pyruvic acid in vivo and in vitro angiogenesis models. Cancer Res 2001, 61: 3290–3293.
- 20 Zheng ZZ, Liu ZX. CD151 gene delivery increases eNOS activity and induces ECV304 migration, proliferation and tube formation. Acta Pharmacol Sin 2007, 28: 66–72.
- 21 Podar K, Tai YT, Davies FE, Lentzsch S, Sattler M, Hideshima T. Vascular endothelial growth factor triggers signaling cascades mediating multiple myeloma cell growth and migration. Blood 2001, 98: 428–435.
- 22 Bian WP, Xu Y, Wang J, Chen F. The antiangiogenesis effect of cryptotanshinone on chick embryo chorioallantoic membrane. J Chinese Microcirculation 2007, 1: 23–26.
- 23 Risau W. Mechanisms of angiogenesis. Nature 1997, 386: 671–674.
- 24 Magdelaine-Beuzelin C, Kaas Q, Wehbi V, Ohresser M, Jefferis R, Lefranc MP, Watier H. Structure-function relationships of the variable domains of monoclonal antibodies approved for cancer treatment. Crit Rev Oncol Hematol 2007, 64: 210–225.
- 25 Bai X, Cerimele F, Ushio-Fukai M, Waqas M, Campbell PM, Govindarajan B, Der CJ et al. Honokiol, a small molecular weight natural product, inhibits angiogenesis in vitro and tumor growth in vivo. J Biol Chem 2003, 278: 35501–35507.
- 26 Don MJ, Liao JF, Lin LY, Chiou WF. Cryptotanshinone inhibits chemotactic migration in macrophages through negative regulation of the PI3K signaling pathway. Br J Pharmacol 2007, 151: 638–646.
- 27 Dittmann K, Gerhauser C, Klimo K, Hamburger M. HPLC-based activity profiling of Salvia miltiorrhiza for MAO A and iNOS inhibitory activities. Planta Med 2004, 70: 909–913.
- 28 Dat NT, Jin X, Lee JH, Lee D, Hong YS, Lee K, Kim YH et al. Abietane diterpenes from Salvia miltiorrhiza inhibit the activation of hypoxia-inducible factor-1. J Nat Prod 2007, 70: 1093–1097.
- 29 Hur JM, Shim JS, Jung HJ, Kwon HJ. Cryptotanshinone but not tanshinone IIA inhibits angiogenesis in vitro. Exp Mol Med 2005, 37: 133–137.