Cell lines

rat sympathetic neurons

Preparation method

Limited solubility in DMSO. 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

10 μM

Applications

Cytarabine apparently induced apoptosis of rat sympathetic neurons at 10 μM, of which 100 μM showed the highest toxicity and killed over 80% of the neurons by 84 hours, involving the release of mitochondrial cytochrome-c and the activation of caspase-3.

Animal models

Pregnant Slc:Wistar rats

Dosage form

Intraperitoneal injection, 250 mg/kg

Application

Cytarabine (250 mg/kg) caused placental growth retardation and increased placental trophoblastic cells apoptosis in the placental labyrinth zone of the pregnant Slc:Wistar rats, which increases from 3 hour after the treatment and peaks at 6 hour before returning to control levels at 48 hour, with remarkably enhanced p53 protein, p53 trancriptional target genes such as p21, cyclinG1 and fas and caspase-3 activity.

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.

Cytarabine (AraC), an analogue of deoxycytidine, is the most effective cytotoxic agent in the treatment of acute myeloid leukemia (AML), which blocks DNA synthesis by inhibiting the function of DNA and RNA polymerases [1].
Cytarabine is incorporated into DNA, it blocks DNA synthesis by inhibiting the function of DNA and RNA polymerases. The most essential step in the AraC activation is phosphorylation into the monophosphate form, which is catalyzed by deoxycytidine kinase (dCK).
In AraC-sensitive rat leukemic cells, sole expression of inactive or spliced dCK forms make a cell resistant to the cytotoxic effects of AraC. It was reported that Ara-C also causes placental growth retardation, induce apoptosis and also impair cell proliferation in the zone of placental labyrinth. By injecting Ara-C into pregnant rats, the placentas were examined from 1 to 48h. the apoptosis of trophoblastic cells in the placental labyrinth zone increased from 3 h after the injecting and then peaked at 6 h and returned to control level at 48 h. Immunoreactivity of p53 protein in the placental labyrinth zone was significantly enhanced and peaked at 3 h after treatment, while no increase in p53 mRNA expression was detected by a reverse transcription polymerase chain reaction [1, 2].
A retrospective analysis was performed in 40 patients which treated with cytarabine 1000 mg/m2/day, mitoxantrone 8 mg/m2/day and etoposide 100 mg/m2/day for five days. 30% of remission rate and 11.2 months of median remission duration was got. In univariate analysis, compared to ≥second relapse (p = 0.02), patients in first relapse had improved overall survival [3].
References:
[1].Veuger MJT, Heemskerk MHM, Honders MW, et al. Functional role of alternatively spliced deoxycytidine kinase in sensitivity to cytarabine of acute myeloid leukemic cells. Blood, 2002, 99(4): 1373-1380.
[2].Yamauchi H, Katayama K, Ueno M, et al. Involvement of p53 in 1-beta-D-arabinofuranosylcytosine-induced trophoblastic cell apoptosis and impaired proliferation in rat placenta. Biology of Reproduction, 2004, 70(6): 1762-1767.
[3]. Liedtke M, Dunn T, Dinner S, et al. Salvage therapy with mitoxantrone, etoposide and cytarabine in relapsed or refractory acute lymphoblastic leukemia. Leukemia Research, 2014, 38(12): 1441-1445.