Drugs affecting the cell cycle via actions on the polyamine metabolic pathway.
Polyamines (putrescine, spermidine, and spermine) are ubiquitous cellular components that have multiple functions, including actions affecting the cell cycle. Polyamine biosynthesis and content is altered during the course of cell cycling via changes in two key biosynthetic enzymes, ornithine decarboxylase and S-adenosyl-methionine decarboxylase. Decreases in polyamine content and/or alterations in the relative amounts of polyamines can be achieved by treatment with inhibitors of these enzymes or by application of polyamine analogues, which subvert mechanisms for polyamine homeostasis and may interfere directly with polyamine-dependent processes. Such changes cause G1 and G2-M cell cycle blocks that can be brought about via induction of p21WAF1/CIP1.
Department of Pharmacology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
Joseph M
JM
Ackermann
Anthony E
AE
Pegg
Diane E
DE
McCloskey
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D015317:Biogenic Polyamines / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000187:drug effects / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D007399:Interphase / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
D015317:Biogenic Polyamines; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004791:Enzyme Inhibitors