Universität zu Köln

Almeida, Meire C., Santos, Ivan C., Paschoalin, Thaysa, Travassos, Luiz R., Mauch, Cornelia, Zigrino, Paola ORCID: 0000-0002-7470-0064, Pesquero, Joao B., Pesquero, Jorge L. and Higuchi, Debora A. (2019). Leucurogin and melanoma therapy. Toxicon, 159. S. 22 - 32. OXFORD: PERGAMON-ELSEVIER SCIENCE LTD. ISSN 0041-0101

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Abstract

Leucurogin is an ECD disintegrin-like protein, cloned from Bothrops leucurus venom gland. This new protein, encompassing the disintegrin region of a PIII metalloproteinase, is produced by recombinant technology and its biological and functional activity was partially characterized in this study. Biological activity was characterized in vitro using human fibroblasts. Functional activity of leucurogin was analysed in vitro and in vivo with murine B16F10 Nex-2 and human melanoma BLM cells. The results show that leucurogin inhibits cellular processes dependent on collagen type I. In a competition assay with collagen, leucurogin inhibits, in a dose-dependent manner, the adhesion of fibroblast to collagen. At 10 mu M leucurogin reduces adhesion (40%) and migration (70%) of hFb and inhibits migration (32%) and proliferation (65%) of BLM cells. At 2.5 mu M leucurogin inhibits 80% cell proliferation of B16F10 Nex-2 melanoma cells. At 4.8 mu M leucurogin inhibits, in vitro, the vascular structures formation by endothelial cells by 66%. Leucurogin, injected intraperitoneally, i.p. (5 mu g/animal, two-month old C57/B16 male mice) on alternate days for 15 days, inhibits lung metastasis of Bl6F10 Nex-2 cells by 70-75%. In the treatment of human melanoma, grafted intradermally in the nude mice flank, leucurogin (7.5 mu g/ kg in alternate days during 17 days) inhibits tumor growth by more than 40%. Leucurogin can be considered a promising agent for melanoma treatment.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Almeida, Meire C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Santos, Ivan C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Paschoalin, Thaysa UNSPECIFIED UNSPECIFIED UNSPECIFIED Travassos, Luiz R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Mauch, Cornelia UNSPECIFIED UNSPECIFIED UNSPECIFIED Zigrino, Paola UNSPECIFIED orcid.org/0000-0002-7470-0064 UNSPECIFIED Pesquero, Joao B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Pesquero, Jorge L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Higuchi, Debora A. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-155941
DOI:	10.1016/j.toxicon.2018.12.005
Journal or Publication Title:	Toxicon
Volume:	159
Page Range:	S. 22 - 32
Date:	2019
Publisher:	PERGAMON-ELSEVIER SCIENCE LTD
Place of Publication:	OXFORD
ISSN:	0041-0101
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language SNAKE-VENOM METALLOPROTEINASE; 3-DIMENSIONAL COLLAGEN LATTICES; BOTHROPS-JARARACA VENOM; CELL-MIGRATION; RECOMBINANT DISINTEGRIN; INTEGRIN ALPHA-2-BETA-1; MATRIX REORGANIZATION; PLATELET-AGGREGATION; MONOCLONAL-ANTIBODY; MALIGNANT-MELANOMA Multiple languages Pharmacology & Pharmacy; Toxicology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/15594