Methylthioadenosine (MTA) inhibits melanoma cell proliferation and in vivotumor growth

BMC Cancer

Research Article

Javier Cortés¹  Matias A Avila²  Rosa Gil³  Juan A Recio³  Judit Grueso³  Anna Pujol³  Pedro Andreu-Pérez³  Teresa Moliné⁴  Javier Hernandez-Losa⁴ 

[1] Clnical Oncology Department, Vall d'Hebron Hospital, 08035, Barcelona, Spain;Division of Hepatology and Gene Therapy, CIMA, University of Navarra, Pamplona, Spain;Medical Oncology Research Program, Vall d'Hebron Research Institute, Vall d'Hebron Institute of Oncology (VHIO) Vall d'Hebron Hospital Barcelona, 08035, Spain;Pathology Department, Vall d'Hebron Hospital Barcelona, 08035, Spain;

关键词: Melanoma;    Melanoma Cell;    Melanoma Cell Line;    Cytostatic Effect;    BRAFV600E Mutation;   

DOI  :  10.1186/1471-2407-10-265

 received in 2010-01-24, accepted in 2010-06-08,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundMelanoma is the most deadly form of skin cancer without effective treatment. Methylthioadenosine (MTA) is a naturally occurring nucleoside with differential effects on normal and transformed cells. MTA has been widely demonstrated to promote anti-proliferative and pro-apoptotic responses in different cell types. In this study we have assessed the therapeutic potential of MTA in melanoma treatment.MethodsTo investigate the therapeutic potential of MTA we performed in vitro proliferation and viability assays using six different mouse and human melanoma cell lines wild type for RAS and BRAF or harboring different mutations in RAS pathway. We also have tested its therapeutic capabilities in vivo in a xenograft mouse melanoma model and using variety of molecular techniques and tissue culture we investigated its anti-proliferative and pro-apoptotic properties.ResultsIn vitro experiments showed that MTA treatment inhibited melanoma cell proliferation and viability in a dose dependent manner, where BRAF mutant melanoma cell lines appear to be more sensitive. Importantly, MTA was effective inhibiting in vivo tumor growth. The molecular analysis of tumor samples and in vitro experiments indicated that MTA induces cytostatic rather than pro-apoptotic effects inhibiting the phosphorylation of Akt and S6 ribosomal protein and inducing the down-regulation of cyclin D1.ConclusionsMTA inhibits melanoma cell proliferation and in vivo tumor growth particularly in BRAF mutant melanoma cells. These data reveal a naturally occurring drug potentially useful for melanoma treatment.

【 授权许可】

Unknown   
© Andreu-Pérez et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.