Methylthioadenosine (MTA) inhibits melanoma cell proliferation and <it>in vivo </it>tumor growth

• Main Authors: Cortés Javier, Pujol Anna, Grueso Judit, Moliné Teresa, Gil Rosa, Hernandez-Losa Javier, Andreu-Pérez Pedro, Avila Matias A, Recio Juan A
• Format: Article
• Language: English
• Published: BMC 2010-06-01
• Series: BMC Cancer
• Online Access: http://www.biomedcentral.com/1471-2407/10/265
• ISSN: 1471-2407

<p>Abstract</p> <p>Background</p> <p>Melanoma 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.</p> <p>Methods</p> <p>To investigate the therapeutic potential of MTA we performed <it>in vitro </it>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 <it>in vivo </it>in a xenograft mouse melanoma model and using variety of molecular techniques and tissue culture we investigated its anti-proliferative and pro-apoptotic properties.</p> <p>Results</p> <p><it>In vitro </it>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 <it>in vivo </it>tumor growth. The molecular analysis of tumor samples and <it>in vitro </it>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.</p> <p>Conclusions</p> <p>MTA inhibits melanoma cell proliferation and <it>in vivo </it>tumor growth particularly in BRAF mutant melanoma cells. These data reveal a naturally occurring drug potentially useful for melanoma treatment.</p>