AICAR (also called acadesine) is a purine nucleoside. Three pharmacological applications of AICAR were identified: i) stimulation under ischemic conditions of the cardiac production of the vasodilator, adenosine [1]; ii) inhibition of hepatic gluconeogenesis at the level of fructose-1,6-bisphosphatase [2], of therapeutic potential in diabetes; and iii) stimulation of AMP-activated protein kinase (AMPK), initially applied to inhibit the hepatic synthesis of triglycerides and cholesterol [3].
AICAR (treated 48 hours) inhibited cell proliferation of mantle cell lymphoma (MCL) cell lines, REC-1, JEKO-1, UPN-1, JVM-2, MAVER-1 and Z-138, with IC50s of 0.28, 0.59, 0.64, 0.98, 0.50, and 0.14 Mm respectively [4]. AICAR inhibited the growth and depletion of pyrimidine nucleotide pools in fibroblasts [5], accelerated repletion of purine nucleotide pools in heart [6], inhibition of fatty acid, sterol synthesis, and gluconeogenesis in hepatocytes, and increase in glucose uptake in muscle [7].
AICAR (500 mg/kg) injected intraperitoneally into C57BL/6J mice 1 hour before LPS administration. LPS induced the expression of TF mRNA in many major organs, including the lung and liver [8]. A daily administration of 400mg/kg AICAR in mice previously inoculated with a MCL xenotransplant significantly reduced tumor burden when compared to control animals, as soon as 7 days of treatment [9].
