Dacogen

Decitabine is indicated for treatment of patients with myelodysplastic syndrome (MDS) . It is a chemical analogue of cytidine, a nucleoside present in DNA and RNA. Cells in the presence of Decitabine incorporate it into DNA during replication and RNA during transcription. The incorporation of Decitabine into DNA or RNA inhibits methyltransferase thereby causing demethylation in that sequence. This adversely affects the way that cell regulatory proteins are able to bind to the DNA/RNA substrate. (In Vitro) :Decitabine treatment significantly inhibits cell growth of SNU719, NCC24 and KATOIII 96 hours after exposure to decitabine. Decitabine induces G2/M arrest and apoptosis in EBVaGC, inhibits invasion ability, and up-regulates E-cadherin expression for EBVaGC.Only high concentrations (10 μM) Decitabine (0.1-1 μM; 24-72 hours) results in a G2 phase arrest, which is accompanied by a reduction of cells in G1 phase.Decitabine up-regulates DCTPP1 and dUTPase expression in HeLa cells. (In Vivo) :Decitabine (1.0 mg/kg, p.o.) in combination with tetrahydrouridine (THU) causes severe toxicity occurs in female CD-1 mice, and results in an increased sensitivity to decitabine toxicity correlating with decitabine plasma levels.Decitabine (1.0 mg/kg; i.p.; once daily for 5 consecutive days) leads to regression of EL4 tumors established in C57BL/6 Mice.