Oxidative stress and inhibition of nitric oxide generation underlie methotrexate-induced senescence in human colon cancer cells

Publication date: Available online 21 July 2017 Source:Mechanisms of Ageing and Development Author(s): Magdalena Dabrowska, Lukasz Uram, Zbigniew Zielinski, Wojciech Rode, Ewa Sikora The response of human colon cancer C85 cells to methotrexate takes the form of reversible growth arrest of the type of stress-induced senescence. In the present study it is shown that during C85 cell progression into methotrexate-induced senescence, dihydrofolate reductase, the primary intracellular target for the drug, is stabilized at the protein level and its enzymatic activity, assayed in crude cellular extracts, decreases by 2-fold. Dihydrofolate reductase inhibition results in an increase in dihydrobiopterin level and an ultimate decrease in the tetrahydrobiopterin: dihydrobiopterin ratio in senescent c...

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