AICAR (Acadesine)

AICAR (Acadesine) (500 μM) increases the ZMP content in extracts of isolated hepatocytes after up to 30-40 min treatment, then remains fairly constant at approximately 4 nmol/g. It causes a transient 12-fold activation of AMPK at 15 min in rat hepatocytes and 2-3 fold activation of AMPK in adipocytes, without affecting levels of ATP, ADP or AMP. This compound also causes a dramatic inhibition of both fatty acid and sterol synthesis in rat hepatocytes, as well as a dramatic inactivation of HMG-CoA reductase. ^[1] It induces apoptosis of B-CLL cells in a dose-dependent manner with EC50 of 380 μM. At 0.5 mM, it decreases cell viability of B-CLL cells from 20 representative patients from 68% to 26%, and induces caspase activation and cytochrome c release from mitochondria. Uptake and phosphorylation of AICAR (0.5 mM) are required to induce apoptosis and activate AMPK in B-CLL cells. While concentrations of 2-4 mM only slightly affect the viability of T cells from B-CLL patients, 0.5 mM remarkedly reduces viability of B cells but not T cells. [2] It triggers loss of cell metabolism in K562, LAMA-84 and JURL-MK1 and is also effective in killing resistant K562 cells and Ba/F3 cells carrying the T315I-BCR-ABL mutation. The effect is abrogated by GF109203X and Ro-32-0432, both inhibitor of classical and new PKCs and accordingly, it triggers relocation and activation of several PKC isoforms in K562 cells. AICAR dose-dependently inhibits K562 colony formation at day 10, the growth inhibitory effect is already detected at 0.25 mM and is maximal at 2.5 mM. ^[3] It causes a concentration-related reduction in CD18 expression on LPS-stimulated neutrophils in vitro. ^[4] At 1 mM, it significantly inhibits N-formyl-methionyl-leucyl-phenylalanine-induced granulocyte CD11b up-regulation by a mean of 61% in blood. ^[5]

AICAR (Acadesine) (50 mg/kg) significantly reduces tumor formation in a mouse xenograft model of K562 cells. ^[3] At 10 mg/kg, this compound results in higher fluid required to stabilize hemodynamics in pigs and inhibits LPS-induced protein permeability of pulmonary capillaries, peak inspiratory pressures on constant tidal volume and dead space ventilation. ^[4]

AICAR (Acadesine) is added to K562 cell lines or primary cells (10³ CD34+ cells/mL) growing in semisolid methyl cellulose medium. MethoCult H4100 or H4236 are used for cell lines and primary CD34+ cells respectively. Colonies are detected after 10 days of culture by adding 1 mg/mL of the MTT reagent and are scored by Image J quantification software.

• https://pubmed.ncbi.nlm.nih.gov/7744080/
• https://pubmed.ncbi.nlm.nih.gov/12522004/
• https://pubmed.ncbi.nlm.nih.gov/19924252/

• https://pubmed.ncbi.nlm.nih.gov/8619186/
• https://pubmed.ncbi.nlm.nih.gov/7877305/

+ 展开