This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Maekawa, R. Articles by Yoshioka, T. Search for Related Content PubMed PubMed Citation Articles by Maekawa, R. Articles by Yoshioka, T.

Correlation of Antiangiogenic and Antitumor Efficacy of N-biphenyl Sulfonyl-phenylalanine Hydroxiamic Acid (BPHA), an Orally-active, Selective Matrix Metalloproteinase Inhibitor

Discovery Research Laboratories, Shionogi and Company, Ltd., 12-4 Sogisu, 5-Chome Fukushima-ku, Osaka 553-0002, Japan [R. M., H. M., H. Y., K. H., H. Ta., T. W., N. U., Y. T., H. K., H. O., H. Ts., Y. K., F. W., K. K., M. O., K. S., T. Y.], and Department of Dermatology, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto 606, Japan [K-i. T.]

ABSTRACT

The antiangiogenic activity and antitumor efficacy of a newly developed matrix metalloproteinase (MMP) inhibitor were examined. N-biphenyl sulfonyl-phenylalanine hydroxiamic acid (BPHA) potently inhibits MMP-2, -9, and -14, but not MMP-1, -3, or -7. In contrast, (-)BPHA, an enantiomer of BPHA, was inactive against all MMPs tested. Daily oral administration of 200 mg/kg BPHA, but not (-)BPHA in mice resulted in potent inhibition of tumor-induced angiogenesis, primary tumor growth, and liver metastasis. The growth inhibition activity of BPHA was 48% and 45% in a B16-BL6 melanoma and F2 hemangio-endothelioma model, respectively. BPHA also showed 42% inhibition of the liver metastasis of C-1H human colon carcinoma cells. These results indicate that selective MMP inhibition is correlated with antiangiogenic and antitumor efficacy and that the selective MMP inhibitor BPHA has therapeutic potential.

This article has been cited by other articles:

				C.-H. Ko, S.-C. Shen, T. J.F. Lee, and Y.-C. Chen Myricetin inhibits matrix metalloproteinase 2 protein expression and enzyme activity in colorectal carcinoma cells Mol. Cancer Ther., February 1, 2005; 4(2): 281 - 290. [Abstract] [Full Text] [PDF]

				A. Robinet, A. Fahem, J.-H. Cauchard, E. Huet, L. Vincent, S. Lorimier, F. Antonicelli, C. Soria, M. Crepin, W. Hornebeck, et al. Elastin-derived peptides enhance angiogenesis by promoting endothelial cell migration and tubulogenesis through upregulation of MT1-MMP J. Cell Sci., January 15, 2005; 118(2): 343 - 356. [Abstract] [Full Text] [PDF]

				T.-W. CHUNG, S.-K. MOON, Y.-C. CHANG, J.-H. KO, Y.-C. LEE, G. CHO, S.-H. KIM, J.-G. KIM, and C.-H. KIM Novel and therapeutic effect of caffeic acid and caffeic acid phenyl ester on hepatocarcinoma cells: complete regression of hepatoma growth and metastasis by dual mechanism FASEB J, November 1, 2004; 18(14): 1670 - 1681. [Abstract] [Full Text] [PDF]

				G. Zhang, C. R. Dass, E. Sumithran, N. Di Girolamo, L.-Q. Sun, and L. M. Khachigian Effect of Deoxyribozymes Targeting c-Jun on Solid Tumor Growth and Angiogenesis in Rodents J Natl Cancer Inst, May 5, 2004; 96(9): 683 - 696. [Abstract] [Full Text] [PDF]

				A. Sgambato, M. Migaldi, M. Montanari, A. Camerini, A. Brancaccio, G. Rossi, R. Cangiano, C. Losasso, G. Capelli, G. P. Trentini, et al. Dystroglycan Expression Is Frequently Reduced in Human Breast and Colon Cancers and Is Associated with Tumor Progression Am. J. Pathol., March 1, 2003; 162(3): 849 - 860. [Abstract] [Full Text] [PDF]

				H. Yamada, F. Saito, H. Fukuta-Ohi, D. Zhong, A. Hase, K. Arai, A. Okuyama, R. Maekawa, T. Shimizu, and K. Matsumura Processing of {beta}-dystroglycan by matrix metalloproteinase disrupts the link between the extracellular matrix and cell membrane via the dystroglycan complex Hum. Mol. Genet., July 1, 2001; 10(15): 1563 - 1569. [Abstract] [Full Text] [PDF]

				M. S. Pepper Role of the Matrix Metalloproteinase and Plasminogen Activator-Plasmin Systems in Angiogenesis Arterioscler Thromb Vasc Biol, July 1, 2001; 21(7): 1104 - 1117. [Abstract] [Full Text] [PDF]

				M. Hidalgo and S. G. Eckhardt Development of Matrix Metalloproteinase Inhibitors in Cancer Therapy J Natl Cancer Inst, February 7, 2001; 93(3): 178 - 193. [Abstract] [Full Text] [PDF]

				M. ELKIN, H.-Q. MIAO, A. NAGLER, E. AINGORN, R. REICH, I. HEMO, H.-L. DOU, M. PINES, and I. VLODAVSKY Halofuginone: a potent inhibitor of critical steps in angiogenesis progression FASEB J, December 1, 2000; 14(15): 2477 - 2485. [Abstract] [Full Text]

				M. Ikeda, R. Maekawa, H. Tanaka, M. Matsumoto, Y. Takeda, Y. Tamura, R. Nemori, and T. Yoshioka Inhibition of Gelatinolytic Activity in Tumor Tissues by Synthetic Matrix Metalloproteinase Inhibitor: Application of Film in Situ Zymography Clin. Cancer Res., August 1, 2000; 6(8): 3290 - 3296. [Abstract] [Full Text]

				J. Kahn, F. Mehraban, G. Ingle, X. Xin, J. E. Bryant, G. Vehar, J. Schoenfeld, C. J. Grimaldi, F. Peale, A. Draksharapu, et al. Gene Expression Profiling in an in Vitro Model of Angiogenesis Am. J. Pathol., June 1, 2000; 156(6): 1887 - 1900. [Abstract] [Full Text] [PDF]