%0 Journal Article
%T Methylthioadenosine (MTA) inhibits melanoma cell proliferation and in vivo tumor growth
%A Pedro Andreu-P¨¦rez
%A Javier Hernandez-Losa
%A Teresa Molin¨¦
%A Rosa Gil
%A Judit Grueso
%A Anna Pujol
%A Javier Cort¨¦s
%A Matias A Avila
%A Juan A Recio
%J BMC Cancer
%D 2010
%I BioMed Central
%R 10.1186/1471-2407-10-265
%X To 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.In 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.MTA 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.Melanoma is a common skin cancer resulting in high morbidity and mortality. The development of effective therapeutics designed to target melanoma has become the recent focus of research to improve the melanoma patient's prognosis.In mammalian cells, 5'-Methylthio-5'deoxyadenosine (MTA) is formed from decarboxylated S-adenosylmethionine in the biosynthesis of spermidine and spermine, and is cleaved by MTA phosphorylase (MTAP) into adenine and 5'-methylthio-5'deoxyribose-1-phospate, which are used for the salvage of ATP and methionine respectively [1].The MTAP gene lies on 9p21, close to the gene CDKN2A that encodes the tumor suppressor proteins p16INK4A and p14ARF being widely expressed in normal cells and tissues [2]. The INK4A-ARF locus on chromosome 9p21, (encoding p16INK4a and p14ARF), is often deleted in human melanoma [3].
%U http://www.biomedcentral.com/1471-2407/10/265