Antitumor Activity of Disintegrin-Like Components from the Venom of Montivipera raddei

Silva Amiryan

.

DOI: 10.4236/jct.2011.25101                

Abstract

Our findings represent the first report of the antitumor activity of the disintegrin-like components from the venom of Armenian viper (M. raddei). The venom of M. raddei was separated by reverse phase high-performance liquid chroma-tography (RP HPLC), and individual fractions were analyzed for disintegrin activity. Disintegrin-like components from the venom of M. raddei, by blocking integrins on breast cancer cells (MDA-MB-435), not only interferes with adhesion of breast cancer cells to the extracellular matrix, but also inhibits cellular mobility which is essential for cancer invasion. These effects seriously curtail the metastatic capability of the MDA-MB-435 cells.

Keywords

Snake Venom, Montivipera raddei (Armenian Viper), Disintegrins, Antitumor Activity

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	D. Hanahan and R. A. Weinberg, “The Hallmarks of Cancer,” Cell, Vol. 100, No. 1, 2000, pp. 57-70. doi:10.1016/S0092-8674(00)81683-9
[2]	F. G. Giancotti and E. Ruoslahti, “Integrin Signaling,” Science, Vol. 285, No. 5430, 1999, pp. 1028-1032. doi:10.1126/science.285.5430.1028
[3]	H. Lodish, A. Berk, L. S. Zipursky, P. Matsudaira, D. Baltimore and J. Darnell, “Molecular Cell Biology,” 5th Edition, Freeman, New York, 2003, p. s973.
[4]	P. C. Brooks, S. Stromblad, R. Klemke, D. Visscher, F. H. Sarkar and D. A. Cheresh, “Antiintegrin Alpha v Beta 3 Blocks Human Breast Cancer Growth and Angiogenesis in Human Skin,” Journal of Clinical Investigation, Vol. 96, No. 4, 1995, pp. 1815-1822. doi:10.1172/JCI118227
[5]	B. Felding-Habermann, T. E. O’Toole, J. W. Smith, E. Fransvea, Z. M. Ruggeri, M. H. Ginsberg, P. E. Hughes, N. Pampori, S. J. Shattil, A. Saven and B. M. Mueller, “Integrin Activation Controls Metastasis in Human Breast Cancer,” Proceedings of the National Academy of Sciences of the USA, Vol. 98, No. 4, 2001, pp. 1853-1858. doi:10.1073/pnas.98.4.1853
[6]	R. Hynes, “Integrins: Versatility Modulation, and Signaling in Cell Adhesion,” Cell, Vol. 69, No. 1, 1992, pp. 11-25. doi:10.1016/0092-8674(92)90115-S
[7]	M. Trikha, Y. A. De Clerk and F. S. Markland, “Contortrostatin, a Snake Venom Disintegrin, Inhibits β1 Integrin-Mediated Human Metastatic Melanoma Cell Adhesion, and Blocks Experimental Metastasis,” Cancer Research, Vol. 54, No. 18, 1994, pp. 4993-4998.
[8]	S. Swenson, F. Costa, W. Ernst, G. Fujii and F. S. Markland, “Contortrostatin, a Snake Venom Disintegrin with Anti-Angiogenic and Anti-Tumor Activity,” Pathophysiol Haemost Thromb, Vol. 34, No. 4-5, 2005, pp. 169-176. doi:10.1159/000092418
[9]	M. A. McLane, E. E. Sanchez, A. Wong, C. Paquette-Straub and J. C. Perez, “Disintegrins,” Current Drug Tar- gets: Cardiovascular and Hematological Disorders, Vol. 4, No. 4, 2004, pp. 327-355. doi:10.2174/1568006043335880
[10]	F. S. Markland, “Snake Venoms and the Hemostatic System,” Toxicon, Vol. 36, No. 12, 1998, pp. 1749-1800. doi:10.1016/S0041-0101(98)00126-3
[11]	M. A. McLane, C. Marcinkiewicz, S. Vijay-Kumar, I. Wierzbicka-Patynowski and S. Niewiarowski, “Viper Venom Disintegrins and Related Molecules,” Proceedings of the Society for Experimental Biology and Medicine, Vol. 219, No. 2, 1998, pp. 109-119.
[12]	C. Marcinkiewicz, “Functional Characteristic of Snake Venom Disintegrins: Potential Therapeutic Implication,” Current Pharmaceutical Design, Vol. 11, No. 7, 2005, pp. 815-827. doi:10.2174/1381612053381765
[13]	N. Moiseeva, R. Bau, S. D. Swenson, F. S. Markland, J.-Y. Choe, Z.-J. Liu and M. Allaire, “Structure of Acostatin, a Dimeric Disintegrin from Southern Copperhead (Agkistrodon cotortrix contortrix), at 1.7 A Resolution,” Acta Crystallographica Section D: Biological Crystallography, Vol. 64, 2008, pp. 466-470. doi:10.1107/S0907444908002370
[14]	C. S. Xu and S. Rahman, “Identification by Site-Directed Mutagenesis of Amino Acid Residues Flanking RGD Motifs of Snake Venom Disintegrins for Their Structure and Function,” Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao (Shanghai), Vol. 33, No. 2, 2001, pp. 153-157.
[15]	R. J. Gould, M. A. Polokoff, P. A. Friedman, T-F. Huang, J. C. Holt, J. J. Cook and S. Niewiarowski, “Disintegrins: A Family of Integrin Inhibitory Proteins from Viper Venoms,” Proceedings of the Society for Experimental Biology and Medicine, Vol. 195, No. 2, 1990, pp. 168-171.
[16]	M. P. Moreno-Murciano, D. Monleón, C. Marcinkiewicz, J. J. Calvete and B. Celda, “NMR Solution Structure of the Non-RGD Disintegrin Obtustatin,” Journal of Molecular Biology, Vol. 329, No. 1, 2003, pp. 135-145. doi:10.1016/S0022-2836(03)00371-1
[17]	S. Bilgrami, S. Yadav, P. Kaur, S. Sharma, M. Perbandt, C. Betzel and T. P. Singh, “Crystal Structure of the Disintegrin Heterodimer from Saw-Scaled Viper (Echis carinatus) at 1.9 A Resolution,” Biochemistry, Vol. 44, No. 33, 2005, pp. 11058-11066. doi:10.1021/bi050849y
[18]	D. Monleon, V. Esteve, H. Kovacs, J. J. Calvete and B. Celda, “Conformation and Concerted Dynamics of the Integrin-Binding Site and the C-terminal Region of Echistatin Revealed by Homonuclear NMR,” Biochemical Journal, Vol. 387, No. 1, 2005, pp. 57-66. doi:10.1042/BJ20041343
[19]	Y. Fujii, D. Okuda, Z. Fujimoto, K. Horii, T. Morita and H. Mizuno, “Crystal Structure of Trimestatin, a Disintegrin Containing a Cell Adhesion Recognition Motif RGD,” Journal of Molecular Biology, Vol. 332, No. 5, 2003, pp. 1115-1122. doi:10.1016/S0022-2836(03)00991-4
[20]	J. Shin, S. Y. Hong, K. Chung, I. Kang, Y. Jang, D. S. Kim and W. Lee, “Solution Structure of a Novel Disintegrin, Salmosin, from Agkistrondon halys Venom,” Biochemistry, Vol. 42, No. 49, 2003, pp. 14408-14415. doi:10.1021/bi0300276
[21]	C. H. Yeh, H. C. Peng and T. F. Huang, “Accutin, a New Disintegrin Inhibits Angiogenesis in Vitro and in Vivo by Acting as Integrin Alphabeta3 Antagonist and Inducing Apoptosis,” Blood, Vol. 92, No. 9, 1998, pp. 3268-3276.
[22]	J. R. Sheu, M. H. Yen, Y. C. Kan, W. C. Hung, P. T. Chang and H. N. Luk, “Inhibition of Angiogenesis in Vitro and in Vivo: Comparison of the Relative Activities of Triflavin, an Arg-Gly-Asp-Containing Peptide and AntiAlpha(v)beta3 Integrin Monoclonal Antibody,” Biochimica et Biophysica Acta, Vol. 1336, No. 3, 1997, pp. 445-454. doi:10.1016/S0304-4165(97)00057-3
[23]	S. I. Kim, K. S. Kim, H. S. Kim, M. M. Choi, D. S. Kim and K. H. Chung, “Inhibition of Angiogenesis by Salmosin Expressed in Vitro,” Oncology Research, Vol. 14, No. 4-5, 2004, pp. 227-233.
[24]	C. H. Yeh, H. C. Peng, R. S. Yang and T. F. Huang, “Rhodostomin, a Snake Venom Disintegrin, Inhibits Angiogenesis Elicited by Basic Fibroblast Growth Factor and Suppresses Tumor Growth by a Selective Alpha(v)beta(3) Blockade of Endothelial Cells,” Molecular Pharmacology, Vol. 59, No. 5, 2001, pp. 1333-1342.
[25]	F. S. Markland, K. Shieh, Q. Zhou, V. Golubkov, R. P. Sherwin and V. Richters, “A Novel Snake Venom Disintegrin that Inhibits Human Ovarian Cancer Dissemination and Angiogenesis in an Orthotopic Nude Mouse Model,” Haemostasis, Vol. 31, No. 3-6, 2001, pp. 183-191.
[26]	Q. Zhou, R. P. Sherwin, C. Parrish, V. Richters, S. G. Groshen, D. Tsao-Wei and F. S. Markland, “Contortrostatin, a Dimeric Disintegrin from Agkistrodon contortrix, Inhibits Breast Cancer Progression,” Breast Cancer Research and Treatment, Vol. 61, No. 3, 2000, pp. 249-260. doi:10.1023/A:1006457903545
[27]	L. A. Repesh, “A New in Vitro Assay for Quantitating Tumor Cell Invasion,” Invasion Metastasis, Vol. 9, No. 3, 1989, pp. 192-208.
[28]	F. G. Giancotti and F. Mainiero, “Integrin-Mediated Adhesion and Signaling in Tumorgenesis,” Biochimica et Biophysica Acta, Vol. 1198, No. 1, 1994, pp. 47-64.