Cyclophosphamide

Cyclophosphamide is a synthetic alkylating agent chemically related to the nitrogen mustards with antineoplastic activity, a immunosuppressant. IC50 & Target:DNA Alkylator^[1] In Vitro: Cyclophosphamide induces outer membrane blebbing, leads to DNA fragmentation, as revealed by TUNEL staining of free 3'-OH DNA ends, and induces cleavage of the caspase 3 and caspase 7 substrate PARP in 9L/P450 cells. Bcl-2 expression fully blocks the activation of both initiator caspases as well as the effector caspase 3 in cells treated with activated Cyclophosphamide. Bcl-2 inhibits the cytotoxic effects but not the cytostatic effects of activated Cyclophosphamide^[1]. Cyclophosphamide inhibits the AChE reversibly with an IC₅₀ of 511 μM^[2]. Carbon tetrachloride does not affect the direct cytotoxicity of cyclophosphamide or 4-hydroxycyclophosphamide to cells in culture^[3].
Cyclophosphamide is a commonly used cross-linking agent that requires metabolic activation. The active metabolite of cyclophosphamide is 4-Hydroperoxycyclophosphamide (HY-117433)^[8][9].
Cyclophosphamide (1-100 μM, 2-3 days) combined with 1% rat liver S9 fraction significantly affected the viability of DT40 cells ^[9].
In Vivo: Cyclophosphamide (injected i.p.;2mg/mouse in 0.1 mL PBS, in C3H mice bearing SW1 tumors) increases the percentage of cells that stained for CD3, CD4 or CD8 in both spleens and tumors^[4].