Mafosfamide Sodium Salt

Mafosfamide sodium salt (Z 7557 sodium salt) targets nuclear DNA, forms DNA cross-links and inhibits DNA synthesis. Mafosfamide sodium salt, a cyclophosphamide analogue, induces apoptosis in lymphoblastoid cells. Mafosfamide sodium salt has antitumor activity[1][2].

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Signaling Pathways >> Cell Cycle/DNA Damage >> DNA/RNA Synthesis

Signaling Pathways >> Cell Cycle/DNA Damage >> DNA Alkylator/Crosslinker

Mafosfamide sodium salt (Z 7557 sodium salt; 2-10 μg/ml; 72 hours) triggers apoptosis in a dose and time dependent manner[1]. Mafosfamide sodium salt (2-10 μg/ml; 24 hours) causes the cells accumulated in S-phase[1]. Mafosfamide sodium salt (10 μg/ml; 24-72 hours) causes p53 stabilization[1]. Mafosfamide sodium salt (10 μg/ml) induces transcriptional inhibition that contributes to the apoptotic response combined with α-amanitin[1]. Apoptosis Analysis[1] Cell Line: TK6 and WTK1 cells Concentration: 2, 10 μg/ml Incubation Time: 72 hours Result: Triggered apoptosis in a dose and time dependent manner. Preferentially induced apoptosis (> 70% of dead cells) in both p53wt and p53mt cells, with necrosis only induced at low levels (< 30% of dead cells). Cell Cycle Analysis[1] Cell Line: TK6 and WTK1 cells Concentration: 2, 10 μg/ml Incubation Time: 24 hours Result: The cells accumulated in S-phase. Western Blot Analysis[1] Cell Line: TK6 and WTK1 cells Concentration: 10 μg/ml Incubation Time: 24, 48, 72 hours Result: Caused p53 stabilization by phosphorylation of Ser15, 20 and 37, and activation of ATM/ATR and Chk1/Chk2.

[1]. Michael Goldstein, et al. Apoptotic Death Induced by the Cyclophosphamide Analogue Mafosfamide in Human Lymphoblastoid Cells: Contribution of DNA Replication, Transcription Inhibition and Chk/p53 Signaling. Toxicol Appl Pharmacol. 2008 May 15;229(1):20-32.

[2]. G Fritz, et al. High-dose Selection With Mafosfamide Results in Sensitivity to DNA Cross-Linking Agents: Characterization of Hypersensitive Cell Lines. Cancer Res. 1997 Feb 1;57(3):454-60.