Azacitidine (5-Azacytidine)

Azacitidine is widely used to demonstrate the correlation between loss of methylation in specifc gene regions and activation of the associated genes. After incorporation into DNA, Azacitidine inhibits DNA methyltransferase noncompetitively, causing a block in cytosine methylation in newly replicated DNA but not in resting, nondividing cells. ^[1] Azacitidine induces differentiation of Friend Erythroleukemia Cell C3H10T1/2 with myotube formation. ^[2] Azacitidine can be activated to the nucleoside triphosphate and incorporate into both DNA and RNA, leading to inhibition of DNA, RNA and protein synthesis in normal eukaryotic cells and in cancer cell lines, which could finally leads to cell death. Azacitidine also inhibits the incorporation of purine metabolites into macromolecules. Azacitidine inhibits the L1210 cells growth with IC50 and of 0.019 μg/mL. ^[3]

Azacitidine inhibits polynucleotide synthesis in leukemic BDF₁ mice. ^[3] Azacitidine (3 mg/kg, i.p.) increases the mean survival time in leukemic BDF1 mice inoculated with Ll210 ascites tumor cells. Azacitidine markedly suppresses all enzymes activity in the polyamine-biosynthetic pathway, including ornithine decarboxylase activity. putrescine-dependent S-adenosyl-L-methionine decarboxylase activity, and spermidine-dependent S-adenosyl-L-methionine decarboxylase activity. Azacitidine also inhibits the accumulations of polyamines in leukemic mice. ^[4]

• Cell lines

  Leukemia L1210 cell

• Concentrations

  0.15 μg/mL

• Incubation Time

  3 days

• Method

  5 mL of L1210 cells (5 × 10³ cells/mL) are incubated with Azacitidine at 37 ℃ for 3 days. Cell number is determined twice a day for 3 days by means of a Model A Coulter counter.

• Animal Models

  BDF1 mice bearing lymphoid leukemia L1210

• Dosages

  3 mg/kg

• Administration

  Daily i.p. injection