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Antimetastatic activity and low systemic toxicity of tetradecyl gallate in a preclinical melanoma mouse model

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Summary

Gallates with eight or more carbon atoms in the lateral chain show potent anticancer activity against various cell lines. However, studies regarding the in vivo antimelanoma activity of tetradecyl gallate (C14) have not yet been reported. In this study an evaluation of the ability of C14 to inhibit metastasis, using lung metastases as a model, was carried out. The experimental mouse melanoma model was established by intravenous injection of metastatic B16F10 melanoma cells. The systemic toxicity of C14 was evaluated in vivo by monitoring the weight, survival, biochemical and hematological parameters, and through histological analysis. It was observed that C14 decreased lung metastasis in vivo by 80% and increased the survival rate of the animals without toxic effects. Additionally, C14 induced cytotoxic effects on B16F10 cells, inhibited the inter-cellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) expression, and significantly decreased cell adhesion. These results reveal that C14 has potent antimetastatic ability and is a good candidate for further study as a potential therapeutic agent for tumor metastases.

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Acknowledgments

This study was supported by grants from CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico), CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior), FAPESC (Fundação de Amparo à Pesquisa de Santa Catarina) and a fellowship from the Universidade do Contestado. This article forms part of the PhD research of Claudriana Locatelli and of Clarissa A. S. de Cordova of the Pharmacy post-graduation course. The research group would also like to thank the Hospital Universitário (HU) for the use of their facilities.

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Correspondence to Tânia Beatriz Creczynski-Pasa.

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Locatelli, C., Carvalho, D.R., Mascarello, A. et al. Antimetastatic activity and low systemic toxicity of tetradecyl gallate in a preclinical melanoma mouse model. Invest New Drugs 30, 870–879 (2012). https://doi.org/10.1007/s10637-010-9628-7

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