Potential anticancer effects of statins: fact or fiction?
Deregulation of any of the steps in cell growth, proliferation and apoptosis may result in its malignant transformation. Statins, along with their lipid-lowering potential, modify several processes in the cell cycle. These agents inhibit cell proliferation and arrest cell cycle progression by interrupting growth-promoting signals. Statins selectively induce proapoptotic protential in tumor cells and synergistically enhance proapoptotic potential of several cytotoxic agents. Statins alter angiogenic potential of cells by modulating apoptosis inhibitory effects of VEGF and decrease secretion of metalloproteases. Statins also alter adhesion and migration of tumor cells, thereby inhibiting tumor invasion and metastasis. Statins suppress rate of activation of multiple coagulation factors and thus prevent coagulation-mediated angiogenesis. Statins have been shown to have anti-tumor activity in experimental models. Various anti-neoplastic properties of statins are probably a result of inhibition of posttranslational modifications of growth regulatory proteins. Molecular mechanisms of antiproliferative, proapoptotic and antiangiogenic effects of statins are reviewed in this chapter.
Kaushal
Varsha
V
Department of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA. kaushalvarsha@uams.edu
Kohli
Manish
M
Mehta
Paulette
P
Mehta
Jawahar L
JL
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects* / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000378:metabolism; D018816:Genes, cdc / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D009362:Neoplasm Metastasis / Q000188:drug therapy / Q000503:physiopathology; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors