Cell lines

Leukemia L1210 cells

Preparation method

The solubility of this compound in DMSO is > 12.2 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 ℃ for several months.

Reacting condition

80 μM; 0 ~ 120 mins

Applications

In leukemia L1210 cells, 5-Azacytidine showed greater inhibition on DNA synthesis instead of RNA synthesis. After a 90-min preincubation, TdR-3H incorporation was inhibited by about 74%, whilst UR-3H incorporation was inhibited by only 32%.

Animal models

BDF1 mice bearing lymphoid leukemia L1210 cells

Dosage form

3 mg/kg; i.p.; q.d.

Applications

In BDF1 mice bearing lymphoid leukemia L1210 cells, 5-Azacytidine increased the mean survival time. Moreover, 5-Azacytidine significantly suppressed all enzymes activity in the polyamine-biosynthetic pathway. In addition, 5-Azacytidine inhibited accumulation of polyamines in leukemic mice.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

5-Azacytidine (also known as 5-AzaC), a compound belonging to a class of cytosine analogues, is a DNA methyl transferase (DNMT) inhibitor that exerts potent cytotoxicity against multiple myeloma (MM) cells, including MM.1S, MM.1R, RPMI-8266, RPMI-LR5, RPMI-Dox40 and Patient-derived MM, with the half maximal inhibition concentration IC50 values of 1.5 μmol/L, 0.7 μmol/L, 1.1 μmol/L, 2.5 μmol/L, 3.2 μmol/L and 1.5 μmol/L respectively [1].

5-Azacytidine incorporates into cellular DNA and/or RNA, subsequently sequesters DNMT and forms a covalent bond between C6 of 5-Azacytidine and cysteine thiolate of DNMTs resulting in depletion of DNMT activity in cells and demethylation of cellular DNA [1].

References:
[1] Kiziltepe T, Hideshima T, Catley L, Raje N, Yasui H, Shiraishi N, Okawa Y, Ikeda H, Vallet S, Pozzi S, Ishitsuka K, Ocio EM, Chauhan D, Anderson KC. 5-Azacytidine, a DNA methyltransferase inhibitor, induces ATR-mediated DNA double-strand break responses, apoptosis, and synergistic cytotoxicity with doxorubicin and bortezomib against multiple myeloma cells. Mol Cancer Ther. 2007 Jun;6(6):1718-27.