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Pemetrexed induces apoptosis in malignant mesothelioma and lung cancer cells through activation of reactive oxygen species and inhibition of sirtuin 1.
Authors: Hwang KE, Kim YS, Hwang YR, Kwon SJ, Park DS, Cha BK, Kim BR, Yoon KH, Jeong ET, Kim HR Abstract Pemetrexed is a multitargeted antifolate used for the treatment of malignant mesothelioma and non-small cell lung cancer (NSCLC). However, the mechanism by which pemetrexed induces apoptosis remains unclear. In the present study, we investigated the involvement of reactive oxygen species (ROS) and sirtuin 1 (SIRT1) in pemetrexed-induced apoptosis in MSTO-211 malignant mesothelioma cells and A549 NSCLC cells. Pemetrexed enhanced caspase-dependent apoptosis, induced intracellular ROS generation, and downregulate...
Source: Oncology Reports - March 5, 2015 Category: Cancer & Oncology Tags: Oncol Rep Source Type: research

Mechanism of Synergy between GMX1777(8) and Pemetrexed
GMX1778 and its prodrug GMX1777 represent a new class of cancer drugs that targets nicotinamide phosphoribosyltransferase (NAMPT) as a new strategy to interfere with biosynthesis of the key enzymatic cofactor NAD, which is critical for a number of cell functions, including DNA repair. Using a genome-wide synthetic lethal siRNA screen, we identified the folate pathway–related genes, deoxyuridine triphosphatase and dihydrofolate reductase, the silencing of which sensitized non–small cell lung carcinoma (NSCLC) cells to the cytotoxic effects of GMX. Pemetrexed is an inhibitor of dihydrofolate reductase currently used to t...
Source: Cancer Research - October 30, 2014 Category: Cancer & Oncology Authors: Chan, M., Gravel, M., Bramoulle, A., Bridon, G., Avizonis, D., Shore, G. C., Roulston, A. Tags: Priority Report Source Type: research

C6 ceramide sensitizes pemetrexed-induced apoptosis and cytotoxicity in osteosarcoma cells.
Abstract Chemotherapy has significantly improved the prognosis of high-grade osteosarcoma (OS), but over 30% of OS patients can still not be cured. Pemetrexed, the newly-developed anti-folate chemotherapy drug, exerted lower efficacy against OS cells. Here, we aimed to increase pemetrexed efficiency, and found that the cell-permeable short-chain ceramide (C6) significantly enhanced pemetrexed-induced viability reduction and death in cultured OS cell lines (U2OS and MG-63). Pemetrexed induced moderate apoptosis in OS cells, which was dramatically augmented by C6 ceramide. The apoptosis inhibitor z-VAD-fmk largely i...
Source: Biochemical and Biophysical Research communications - August 21, 2014 Category: Biochemistry Authors: Zhu X, Du X, Deng X, Yi H, Cui S, Liu W, Shen A, Cui Z Tags: Biochem Biophys Res Commun Source Type: research

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