Polyamines are essential for normal cell growth and function, interacting with various macromolecules through electrostatic and covalent bonds. Their metabolism is complex, with multiple regulatory mechanisms to maintain homeostasis. Polyamines are critical for cell survival and have been linked to human diseases, with success in treating parasitic infections. Targeting the polyamine pathway for cancer treatment has had limited success, though drugs like DFMO have shown promise in chemoprevention. Recent developments in polyamine analogues have improved understanding of their role in inducing apoptosis in cancer cells. Polyamines are cations that interact with DNA and RNA, influencing gene expression and transcription. They also interact with acidic phospholipids in membranes, affecting membrane rigidity and acting as antioxidants. Polyamines regulate several membrane-bound enzymes, including adenylate cyclase and ion channels. Polyamine metabolism in eukaryotic cells involves six enzyme reactions, starting with the synthesis of putrescine from ornithine, followed by the production of spermidine and spermine. Key enzymes include ODC, SSAT, and PAO, which regulate polyamine levels through synthesis, retroconversion, and catabolism. These enzymes are tightly regulated at multiple levels, including transcription, translation, and post-translational modifications. Polyamines are transported into and out of cells, with export being regulated by cell growth status. The major polyamines exported are N1-acetylspermidine and putrescine. Inhibitors of polyamine metabolism have been developed, but their effectiveness in treating diseases is limited. ODC is a key regulatory enzyme, with its activity regulated by feedback mechanisms involving polyamines and the antizyme (AZ) protein. AZ binds to ODC and targets it for degradation, while the antizyme inhibitor (AZI) can release ODC from AZ. Three forms of AZ have been identified, each with specific roles in polyamine metabolism. SSAT and PAO are involved in polyamine catabolism, producing hydrogen peroxide, which can induce cell death. The regulation of SSAT is influenced by polyamine analogues, with superinduction leading to increased SSAT activity. PAO activity is also regulated, with increased activity in response to growth inhibition and cancer cell density. Polyamines regulate cell growth and death, with their concentrations influencing cell cycle progression through interactions with cyclins and cyclin-dependent kinases. High polyamine levels can promote cell growth, while depletion can induce apoptosis. However, the relationship between polyamine levels and cell death is complex, with polyamines also acting as protective agents against oxidative stress. DFMO, a polyamine inhibitor, has shown limited success in cancer treatment due to compensatory mechanisms that maintain polyamine homeostasis. However, it has been effective in treating parasitic infections. Recent studies suggest that DFMO may have potential in chemoprevention, with low-dose administration showing prolonged polyamine depletion.Polyamines are essential for normal cell growth and function, interacting with various macromolecules through electrostatic and covalent bonds. Their metabolism is complex, with multiple regulatory mechanisms to maintain homeostasis. Polyamines are critical for cell survival and have been linked to human diseases, with success in treating parasitic infections. Targeting the polyamine pathway for cancer treatment has had limited success, though drugs like DFMO have shown promise in chemoprevention. Recent developments in polyamine analogues have improved understanding of their role in inducing apoptosis in cancer cells. Polyamines are cations that interact with DNA and RNA, influencing gene expression and transcription. They also interact with acidic phospholipids in membranes, affecting membrane rigidity and acting as antioxidants. Polyamines regulate several membrane-bound enzymes, including adenylate cyclase and ion channels. Polyamine metabolism in eukaryotic cells involves six enzyme reactions, starting with the synthesis of putrescine from ornithine, followed by the production of spermidine and spermine. Key enzymes include ODC, SSAT, and PAO, which regulate polyamine levels through synthesis, retroconversion, and catabolism. These enzymes are tightly regulated at multiple levels, including transcription, translation, and post-translational modifications. Polyamines are transported into and out of cells, with export being regulated by cell growth status. The major polyamines exported are N1-acetylspermidine and putrescine. Inhibitors of polyamine metabolism have been developed, but their effectiveness in treating diseases is limited. ODC is a key regulatory enzyme, with its activity regulated by feedback mechanisms involving polyamines and the antizyme (AZ) protein. AZ binds to ODC and targets it for degradation, while the antizyme inhibitor (AZI) can release ODC from AZ. Three forms of AZ have been identified, each with specific roles in polyamine metabolism. SSAT and PAO are involved in polyamine catabolism, producing hydrogen peroxide, which can induce cell death. The regulation of SSAT is influenced by polyamine analogues, with superinduction leading to increased SSAT activity. PAO activity is also regulated, with increased activity in response to growth inhibition and cancer cell density. Polyamines regulate cell growth and death, with their concentrations influencing cell cycle progression through interactions with cyclins and cyclin-dependent kinases. High polyamine levels can promote cell growth, while depletion can induce apoptosis. However, the relationship between polyamine levels and cell death is complex, with polyamines also acting as protective agents against oxidative stress. DFMO, a polyamine inhibitor, has shown limited success in cancer treatment due to compensatory mechanisms that maintain polyamine homeostasis. However, it has been effective in treating parasitic infections. Recent studies suggest that DFMO may have potential in chemoprevention, with low-dose administration showing prolonged polyamine depletion.