Adenosine dialdehyde (AdOx), an indirect inhibitor that can be incorporated by cells. AdOx inhibits S-adenosyl-L-homocystein hydrolase, resulting in the accumulation of S-adenosyl-L-homo cystein (Adoicy), a product inhibitor of methyltransferases that utilize S-adenosyl-L-methionine (AdoMet) as the methyl group donor. AdOx inhibited the Tax-activated NF-κB pathway, resulting in reactivation of p53 and induction of p53 target genes. Analysis of the NF-κB pathway demonstrated that AdOx treatment resulted in degradation of the IκB kinase complex and inhibition of NF-κB through stabilization of the NF-κB inhibitor IκBα. AdOx induced G2/M cell cycle arrest and cell death in HTLV-1-transformed but not control lymphocytes.
In vivo
AdOx exerts a potent inhibitory effect on the in situ growth of established murine neuroblastoma (MNB) tumors, prolongs the life span of tumor bearing mice, and does not suppress hematopoiesis when administered by steady state infusion. AdOx inhibits the replication of L1210 leukemia cells and increased life span approximately 40% when administered i.p. at a dose of 20 mg/kg/day until death.
