Extracts of Aster species Inhibit Invasive Phenotype and Motility of H-ras MCF10A Human Breast Epithelial Cells Possibly via Downregulation of MMP-2 and MMP-9

  • Ahn, Seong-Min (College Pharmacy, Duksung Womens University) ;
  • Lee, Kang-Ro (Natural Products Laboratory, College of Pharmacy, SungKyunKwan University) ;
  • Moon, A-Ree (College Pharmacy, Duksung Womens University)
  • Published : 2002.12.01


Cancer metastasis represents the most important cause of cancer death and antitumor agents that may inhibit this process have been extensively pursued. Invasion and metastasis of malignantly transformed cells involve degradation of the extracellular matrix (ECM) components by matrix metalloproteinases (MMP), especially MMP-2 and -9. We previously showed that H-ras-induced invasive phenotype may involve MMP-2, rather than MMP-9, in MCF10A cells. In the present study, we investigated the chemopreventive effect of Aster, a widely used culinary vegetable in Korea. We screened twelve extracts from three Aster species (Aster scaber, Aster oharai and Aster glehni) for the inhibitory effect on MMP activities of H-ras MCF10A human breast epithelial cells. All of the extracts tested in this study efficiently inhibited the gelatinolytic activities of MMP-2 and MMP-9. A more prominent inhibition was observed in MMP-2 activity compared to MMP-9. Out of twelve extracts, eight extracts showed>90% inhibition of MMP-2 activity in H-ras MCF10A cells while only one extract showed>90% inhibition of MMP-9 activity. We selected three extracts (AO-3, AG-3 and AS-EA) for further studies since they exerted a marked inhibition in the ratio of MMP-2 to MMP-9. Treatment with AO-3, AG-3 and AS-EA in H-ras MCF10A cells caused a significant inhibition of invasive phenotype and migration, proving a chemopreventive potential of these extracts. Taken together, our results demonstrate that extracts of Aster effectively inhibit invasion and migration of highly malignant human breast cells, possibly via downregulation of MMP-2 and MMP-9.


  1. Brown, P.D. (1999). Clinical studies with matrix metalloproteinases inhibitors. APMTS. 107, 174-180
  2. Ferguson, L.R. (1994). Antimutagens as cancer chemopreventive agents in the diet. Mut. Res. 307, 395-410 https://doi.org/10.1016/0027-5107(94)90313-1
  3. Gesa, M., Aathony, D.W. and Gabriele, M.K. (1999). Planta Medica. 65, 493-506 https://doi.org/10.1055/s-1999-14004
  4. Hur, J.Y., Soh, Y., Kim, B.H., Suk, K., Sohn, N.W., Kim, H.C., Kwon, H.C., Lee, K.R. and Kim, S.Y. (2001). Neuroprotective and neurotrophic effects of quinic acids from Aster scaber in PC12 cells. Biol. Phwn. Bull. 24, 921-4
  5. Jozaki, K., Marucha, P.T., Despins, A.W. and Kreutzer, D.L. (1990). An in vitro model of cell migration: Evaluation of vascular endothelial cell migration Anal. Biochem. 190, 39-47
  6. Kahari, V.M. and Saarialho-Kcre, U. (1997). Matrix metalloprotemases in skin. Exp. Dermatol. 6, 199-213
  7. Kim, C.M., Sin, M.K., An, T.K., Lee, K.S. and Lee, K.S. (ed.) (1997). 'Dictionary of Chinese Herb.' JungDam publisher, Seoul, p. 1431
  8. Kim, M.S. Son, M. W., Kim, W. B., Park, Y. I., and Moon, A. (2000). Apicidin, an inhibitor of histone deacetylase, prevents H-ras-induced invasive phenotype. Cancer Lett. 157, 23-30 https://doi.org/10.1016/S0304-3835(00)00465-1
  9. Lee, T.-B. (1989). 'Illustrated Flora of Korea.' HyangMun. Publications, Seoul, p. 760
  10. Liotta, L.A., Steeg, P-S. and Sletler-Stevenson, W.G. (1991). Canccr metastasis and angiogenesis: an imbalance of positive and negative regulation. Cell. 64, 327-336 https://doi.org/10.1016/0092-8674(91)90642-C
  11. Mahmood, N., Piacente, S., Burke, A., Khan, A. and Pizza, C. (1997). Antiviral Chemistry & Chemotherapy. 8, 70-74 https://doi.org/10.1177/095632029700800108
  12. Moon, A., Kim, M.S., Kim, T.G., Kim, S.H., Kim, H.E., Chen, Y.Q., and Kim, H. R. C. (2000). H-ras, but not N-ras, induces an invasive phenotype in human breast epithelial cells: A role for MMP-2 in the H-ras induced invasive phenotype. Int. J. Cancer. 85, 176-81 https://doi.org/10.1054/bjoc.2001.1880
  13. Stavric B. (1994). Role of chemopreventers in human diet. Clinical Biochem. 27, 319-32 https://doi.org/10.1016/0009-9120(94)00039-5
  14. Stetler-Stevenson, W.G. (1990). Type-IV collagenases in tumor invasion and metastasis. Cancer Metastasis Rev. 9, 289-303 https://doi.org/10.1007/BF00049520
  15. Stctler-Stevenson, W.G., Aznavoohan, S. and Liotta, L.A (1993). Tumor cell interactions with die extracellular matrix during invasion and metastasis. Annu. Rev. Cell Biol. 9, 541- 573 https://doi.org/10.1146/annurev.cb.09.110193.002545
  16. Stetler-Stevenson, W.G. (1999). Matrix metalloproteinases in angiogenesis: a moving target for therapeutic intervention. J. Clin. Invest. 103, 1237-1241 https://doi.org/10.1172/JCI6870
  17. Tryggvason, K., Hoyhtya, M., and Pyke, C. (1993). Type IV collagenase in invasive tumors. Breast Cancer Res. Treat. 24, 209-218
  18. Ura, S.H., Bonfil, R.D., Reich, R., Reddel, R., Pfeifer, A., Hiris, C.C. and Klein-Szanto, A.J. (1989). Expression of type IV collagenase and procollagen genes and its correlation with the tumorigenic, invasive, and metastatic abilities of oncogenc-transformed human bronchial epithelial cells. Cancer Res. 49, 4615-4621
  19. Werb, Z., Vu, T.H., Rinkenberger, J.L. and Coussens, L.M. (1999). Matrix-degrading proteases and angiogenesis during development and tumor formation. APMIS. 107, 11-18 https://doi.org/10.1111/j.1699-0463.1999.tb01521.x
  20. Yip, D., Ahmad, A., Karapetis, C.S., Hawkins, C.A. and Harper, P.G. (1999). Matrix metalloproteinase inhibitors: applications in oncology, Invest. New Dmgs. 17, 387-399