Alternative approaches to improve the treatment of advanced
melanomas are highly needed. The
disintegrin domain of
metalloproteinases binds
integrin receptors on
tumor cells, blocking migration, invasion, and metastatization. Previous studies showed that
jararhagin, from the Bothrops jararaca
snake venom, induces changes in the morphology and viability of SK-Mel-28 human
melanoma cells, and decreases the number of
metastases in mice injected with pre-treated cells. The purpose of this study was to evaluate the molecular effects of
jararhagin on SK-Mel-28 cells and fibroblasts, concerning the expression of
integrins,
cadherins,
caspases, and TP53 genes. Sub-toxic doses of
jararhagin were administered to confluent cells. RT-PCR was performed following extraction of total
RNA.
Jararhagin treatments induced similar morphological alterations in both normal and
tumor cells, with higher IC50 values for fibroblasts.
Integrin genes were downregulated in untreated cells, except for ITGA6a,b, ITGAv, and ITGB3 which were highly expressed in SK-Mel-28. The
integrin expression profiles were not affected by the toxin. However,
jararhagin 30ng/μl upregulated genes TP53, CDKN1A, CDKN2A,
CASP3, CASP5, CASP6, CASP8, and E-CDH in SK-Mel-28, and genes ITGB6, ITGB7,
CASP3, TP53, and CDKN1B in fibroblasts. Appropriate
jararhagin concentration can have apoptotic and suppressant effects on SK-Mel-28 cells, rather than on fibroblasts, and can be used to develop potential anti-
cancer drugs.