Effect of Ethanol Extract from Salvia miltiorrhiza on Chemoprevention and Metastasis of Breast Cancer

단삼 에탄올추출물이 유방암 예방 및 전이에 미치는 영향

  • Shon, Yun-Hee (Intractable Diseases Research Center, Dongguk University) ;
  • Cho, Hyun-Jung (Intractable Diseases Research Center, Dongguk University) ;
  • Kim, Mee-Kyung (Intractable Diseases Research Center, Dongguk University) ;
  • Jung, Eun-Jung (Department of Pharmacology, College of Medicine, Dongguk University) ;
  • Nam, Kyung-Soo (Department of Pharmacology, College of Medicine, Dongguk University)
  • 손윤희 (동국대학교 난치병한양방치료연구소) ;
  • 조현정 (동국대학교 난치병한양방치료연구소) ;
  • 김미경 (동국대학교 난치병한양방치료연구소) ;
  • 정은정 (동국대학교 의과대학 약리학교실) ;
  • 남경수 (동국대학교 의과대학 약리학교실)
  • Published : 2007.03.31

Abstract

Ethanol extract from Salvia miltiorrhiza (SME) was tested for breast cancer chemoprevention and metastasis by measuring the activites of cytochrome P45O 1A1, aromatase, ornithine decarboxylase (ODC), and matrix metalloproteinase (MMP)-9. SME significantly inhibited cytochrome P45O 1A1-mediated ethoxyresorufin O-deethylase (EROD) activity in a dose-dependent manner in a concentration range of 100${\sim}$l,200 ${\mu}g/ml$ (p<0.01). Microsomal aromatase (estrogen synthase) activity was suppressed 54.9%${\sim}$77.5% by the SME at concentration of 600${\sim}$l,200 ${\mu}g/ml$. ODC activity induced by 12-O-tet-radecanoylphorbol-13-acetate (TPA) was significantly reduced by the SME 900 and 1,200 ${\mu}g/ml$ (p<0.05) in MCF-7 breast cancer cells. In addition, SME (900 and 1,200 ${\mu}g/ml$) markedly inhibited MMP-9 activity, a key role in cancer metastasis. Therefore, SME is worth further investigation with respect to breast cancer chemoprevention or therapy.

Keywords

References

  1. Zhou, C., Zhou, D., Esteban, J., Murai, J., Sitteri, P. K., Wilczynski, S. and Chen, S. (1996) Aromatase gene expression and its exon I usage in human breast tumors. Detection of aromatase messenger RNA by reverse trnsription-polymerase chain reaction (RT-PCR). J. Steroid Biochem. Mol. Biol. 59: 163-171 https://doi.org/10.1016/S0960-0760(96)00100-8
  2. Forrester, L. M., Hates, J. D., Millis, R., Barnes, D., Harris, A. L., Schlager, J. J., Powis, G. and Wolf, C. R. (1990) Expression of glutathione S-transferases and cytochrome P450 in normal and tumor breast tissue. Carcinogenesis 11: 2163-2170 https://doi.org/10.1093/carcin/11.12.2163
  3. Li, L., Carol, T. and Susan, K. G. (2000) Inhibition of ornithine decarboxylase decreases tumor vascularization and reverse spontaneous tumors in ODC/Ras transgenic mice. Cancer Res. 60: 5696-5730
  4. Huber, M. and Poulin, R. (1996) Permissive role of polymines in the cooperative action of estrogens and insulin or insulin-like growth factor I on human breast cancer cell growth. J. Clin. Endocrinol. Metab. 81: 113-123 https://doi.org/10.1210/jc.81.1.113
  5. Chambers, A. F. and Matrisian, L. M. (1997) Changing views of the role of matix metalloproteinases in metastasis. J. Natl. Cancer Inst. 89: 1260-1270 https://doi.org/10.1093/jnci/89.17.1260
  6. Chang, C. and Werb, Z. (2001) The many faces of metalloproteases: cell growth, invasion, angiogenesis and metastasis. Trends Cell Biol. 11: s37-s42
  7. Hong, M. K., Cho, K. Y., Oh, S. J., Kim, K. M. and Yu, S. J. (2002) Implication of the activation of matrix metalloproteinase- 2 on the metastasis in breast cancer. J. Korea Surg. Soc. 62: 18-25
  8. Mok, J. S., Kim, Y. M., Kim, S. H. and Chang, D. S. (1995) Antimicrobial property of the ethanol extract from Salvia miltiorrhiza. J. Food Hyg. Safety 10: 23-28
  9. Lee, Y. J. and Lee, S. Y. (1992) Parmacognosy, 131-137, Dong Myeung Sa, Seoul, Korea
  10. Kim, O. H., Chung, S. Y., Park, M. K., Rheu, H. M. and Yang, J. S. (1999) Anticancer activity of natural products including Salvia miltiorrhiza. J. Appl. Pharmacology 7: 29- 34
  11. Pohl, R. J. and Fouts, J. R. (1980) A rapid method for assaying the metabolism of 7-ethoxyresorufin by microsomal subcellular fractions. Anal. Biochem. 107: 150-155 https://doi.org/10.1016/0003-2697(80)90505-9
  12. Rodrigues, A. D. and Prough, R. A. (1991) Induction of cytochromes P450 1A1 and P450 1A2 and measurement of catalytic activities. Methods Enzymol. 206: 423-431 https://doi.org/10.1016/0076-6879(91)06111-F
  13. Thompson, E. A. and Siiteri, P. K. (1974) Utilization of oxygen and reduced nicotinamide adenine dinucleotide phosphate by human placental microsomes during aromatization of androstenedione. J. Biol. Chem. 249: 5364-5372
  14. Nam, K. S., Son, O. L., Lee, K., H., Cho, H. J. and Shon, Y. H. (2004) Effect of Cnidii Rhizoma on profliferation of breast cancer cell, nitric oxide production and ornithine decarboxylase activity. Kor. J. Pharmacogn. 35: 283-287
  15. Overall, C. M., Wrana, J. L. and Soddek, J. (1989) Independent regulation of collagenase, 72 kDa progelatinase, and metalloendoproteinase inhibitor expression in human fibroblasts by transforming growth factor-beta. J. Biol. Chem. 264: 1860-1869
  16. Manni, A., Astrow, S. H., Gammon, S., Thompson, J., Mauger, D. and Washington, S. (2001) Immunohistochemical detection of ornithinedecarboxylase in primary and metastaic human breast cancer specimens. Breast Cancer Res. Treat. 67: 147-156 https://doi.org/10.1023/A:1010697218986
  17. David, L. and Nesland, J. M. (1994) Expression of laminin, collagen, fibronectin, and type clooagenase in gastric carcinoma. Cancer 73: 518-527 https://doi.org/10.1002/1097-0142(19940201)73:3<518::AID-CNCR2820730305>3.0.CO;2-T
  18. Rha, S. Y., Kim, J, M., Roh, J. K., Lee, K. S., Min, J. S., Kim, B. S. and Chung, H. C. (1997) Sequential production and activation of matrix metalloproteinase-9 with breast cancer progression. Breast Cancer Res. Treat. 43: 175-181 https://doi.org/10.1023/A:1005701231871