Agmatine modulates the in vivo biosynthesis and interconversion of polyamines and cell proliferation

The arginine metabolite agmatine protects mitochondrial function and confers resistance to cellular apoptosis

“…The growth-suppressive effects of agmatine may be due to a decrease in the mitotic rate, an increase in cell death, or both. We and others have shown that the administration of agmatine suppresses the mitotic rate by measuring [ 3 H]thymidine incorporation in several cell lines (16,53,59) and in vivo (32). Agmatine is not toxic to any cell lines at the doses administered, as determined by trypan blue exclusion (data not shown).…”

“…Initial studies on apoptosis in thymocytes observed polyamine depletion as an unsuspected finding and hypothesized that polyamine depletion contributed to the activation of apoptosis (25). Agmatine depletes intracellular polyamine levels to suppress growth (4,16,22,29,46,59,68). Supplementation with the polyamine putrescine attenuates this effect (22,33,59).…”

“…Agmatine suppresses growth through the reduction of intracellular polyamine levels, which are required for growth, and inhibition of ornithine decarboxylase (ODC), the first and rate-limiting enzyme of polyamine biosynthesis, in all models studied to date (4,16,22,29,46,59,68). Reduction of cellular polyamine levels occurs by the induction of the polyamine autoregulatory protein antizyme (4,29,59), increasing activity of polyamine catabolism (16,68), and/or decreasing ODC activity by another mechanism, possibly by reduction of ODC translation (4,71). Furthermore, agmatine is transported into mammalian cells via the polyamine transport system (57).…”

Molecular Basis for the Antiproliferative Effect of Agmatine in Tumor Cells of Colonic, Hepatic, and Neuronal Origin

“…at ASPET Journals on May 10, 2018 molpharm.aspetjournals.org the intracellular levels of the polyamines (Satriano et al, 1998;Choi and Cho, 1999;Vargiu et al, 1999;Babal et al, 2001;Dudkowska et al, 2003;Higashi et al, 2004;Mayeur et al, 2005). ODC-antizyme induction has been supposed to be the main mechanism underlying agmatine's action, because negative regulation of the polyamine forming enzyme ornithine decarboxylase by agmatine was found to be paralleled by an induction of ODC-antizyme in some cell lines and tissues (Dudkowska et al, 2003;Gardini et al, 2003;Higashi et al, 2004).…”

“…Agmatine administration to tumor cells in vitro results in a suppression of cell proliferation (Satriano et al, 1998;Choi and Cho, 1999;Vargiu et al, 1999;Babal et al, 2001;Dudkowska et al, 2003;Higashi et al, 2004;Kribben et al, 2004;Molderings et al, 2004;Mayeur et al, 2005). At the intracellular level, agmatine-induced decrease of cell proliferation was shown to be due to a decrease in the intracellular levels of the polyamines putrescine, spermidine, and spermine (Satriano et al, 1998;Choi and Cho, 1999;Vargiu et al, 1999;Babal et al, 2001;Dudkowska et al, 2003;Higashi et al, 2004;Mayeur et al, 2005), which are pivotal for cell growth (Igarashi and Kashiwagi, 2000). The intracellular concentration of polyamines is controlled at several stages, including their biosynthesis and their uptake.…”