Sugarcane Cystatin CaneCPI-4 inhibits Melanoma Growth by Angiogenesis Disruption
Juliana P Oliveira1, Helena F Magliarelli1, Felipe V Pereira2, Andréia Gianotti3, Andréa Soares-Costa3, Flavio Henrique-Silva3, Alda Wakamatsu4, Iberê C Soares4, Suely Nonogaki5, Luiz R Travassos2, Adriana K Carmona1 and Thaysa Paschoalin2*
- *Corresponding Author:
- Dr. Thaysa Paschoalin
Unidade de Oncologia Experimental
Departamento de Microbiologia
Imunologia e Parasitologia
Universidade Federal de São Paulo (UNIFESP)
Rua Botucatu, 862, 8º andar
São Paulo, SP 04023-062, Brazil
E-mail: [email protected]
Received Date: August 09, 2011; Accepted Date: September 07, 2011; Published Date: September 15, 2011
Citation: Oliveira JP, Magliarelli HF, Pereira FV, Gianotti A, Soares-Costa A, et al. (2011) Sugarcane cystatin CaneCPI-4 inhibits Melanoma Growth by Angiogenesis Disruption. J Cancer Sci Ther 3: 161-167. doi:10.4172/1948-5956.1000081
Copyright: © 2011 Oliveira JP, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Study background: Cathepsins are lysosomal cysteine proteases that have increased expression in tumor cells, may translocate to the cell surface and be secreted. They play a role in tumor angiogenesis. Cystatins are natural cysteine protease inhibitors that can inhibit tumor development, growth and metastasis. In the present work we evaluated the potential therapeutic use of sugarcane cystatin CaneCPI-4 as an anticancer drug. Methods: Viability, migration, invasion and anchorage-independent growth were investigated in B16F10-Nex2 melanoma and HUVEC cells in the presence of CaneCPI-4. The in vivo effect of CanceCPI-4 on tumor development was assessed using a murine model. Angiogenesis in vitro was evaluated using HUVEC cells plated on Matrigel. Immunohistochemical analysis of CD34 expression in primary melanoma was also carried out. Results: Sugarcane cystatin CaneCPI-4 was not cytotoxic to melanoma or HUVEC cells growing in vitro, but efficiently inhibited melanoma cell development in vivo. CaneCPI-4 inhibited melanoma and endothelial cell migration and tumor invasion in vitro. Using a Matrigel angiogenesis assay, CaneCPI-4 at 1 mM was able to completely abolished endothelial cell sprouting in vitro. Angiogenesis inhibition was confirmed in vivo by immunohistochemistry. Conclusions: Sugarcane cystatin CaneCPI-4 inhibits melanoma development in vivo by angiogenesis disruption and inhibition of melanoma invasion, migration and anchorage-independent growth.