Targeting Ras signaling through inhibition of carboxyl methylation: An unexpected property of methotrexate

@article{WinterVann2003TargetingRS,
  title={Targeting Ras signaling through inhibition of carboxyl methylation: An unexpected property of methotrexate},
  author={Ann M. Winter-Vann and Barton A. Kamen and Martin O. Bergo and Stephen G. Young and Stepan Melnyk and S. Jill James and Patrick J. Casey},
  journal={Proceedings of the National Academy of Sciences of the United States of America},
  year={2003},
  volume={100},
  pages={6529 - 6534}
}
  • A. Winter-Vann, B. Kamen, +4 authors P. Casey
  • Published 15 May 2003
  • Biology, Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
The antifolate methotrexate is one of the most successful drugs in cancer chemotherapy. Although its efficacy is widely attributed to a decrease in nucleotide biosynthesis (1), methotrexate is known to increase homocysteine (2), a compound associated with an elevated risk of heart disease, Alzheimer's disease (3), and neural tube defects (4). A potential mechanism for the detrimental effects of homocysteine is cellular hypomethylation from an increase in S-adenosylhomocysteine (5), an inhibitor… Expand
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