%0 Journal Article
%T Molecular mechanism implicated in Pemetrexed-induced apoptosis in human melanoma cells
%A Aitziber Buqu¨¦
%A Jangi Sh Muhialdin
%A Alberto Mu£¿oz
%A Bego£¿a Calvo
%A Sergio Carrera
%A Unai Aresti
%A Aintzane Sancho
%A Itziar Rubio
%A Guillermo L¨®pez-Vivanco
%J Molecular Cancer
%D 2012
%I BioMed Central
%R 10.1186/1476-4598-11-25
%X In the current work we studied the effect of MTA on four human melanoma cell lines A375, Hs294T, HT144 and MeWo and in two NSCLC cell lines H1299 and Calu-3. We have found that MTA induces DNA damage, S-phase cell cycle arrest, and caspase- dependent and ¨Cindependent apoptosis. We show that an increment of the intracellular reactive oxygen species (ROS) and p53 is required for MTA-induced cytotoxicity by utilizing N-Acetyl-L-Cysteine (NAC) to blockage of ROS and p53-defective H1299 NSCLC cell line. Pretreatment of melanoma cells with NAC significantly decreased the DNA damage, p53 up-regulation and cytotoxic effect of MTA. MTA was able to induce p53 expression leading to up-regulation of p53-dependent genes Mcl-1 and PIDD, followed by a postranscriptional regulation of Mcl-1 improving apoptosis.We found that MTA induced DNA damage and mitochondrial-mediated apoptosis in human melanoma cells in vitro and that the associated apoptosis was both caspase-dependent and ¨Cindependent and p53-mediated. Our data suggest that MTA may be of therapeutic relevance for the future treatment of human malignant melanoma.
%K Pemetrexed
%K MTA
%K Antifolates
%K DNA damage
%K Apoptosis
%K Melanoma
%U http://www.molecular-cancer.com/content/11/1/25/abstract