Fenofibrate in cancer: mechanisms involved in anticancer activity

摘要: Objective:  To review the mechanisms of anti-cancer activity fenofibrate (FF) and other Peroxisome Proliferator Activator Receptor α (PPARα) agonists based on evidences reported in published literature. Methods:  We extensively reviewed literature concerning FF as an off target drug. Controversies regarding conflicting findings were also addressed. Results: The main mechanism involved is anti-angiogenesis through down-regulation  Vascular Endothelial Growth Factor (VEGF), Vascular (VEGFR) Hypoxia Inducible factor-1 (HIF-1α), inhibition endothelial cell migration, up-regulation endostatin thrombospondin-1, but there are many contributing like apoptosis cycle arrest, Nuclear Kappa B (NF-kB) Protein kinase (Akt) decrease cellular energy by impairing mitochondrial function. impairment related to Phospho-Inositol 3 Kinase (PI3K)/Akt axis p38 map (MAPK) cascade. A possible role should be assigned stimulated over-expression Tribbles Homolog-3 (TRIB3) which inhibits Akt phosphorylation. Important anti-metastatic activities due MCP-1 (monocyte chemotactic protein-1), decreased Metalloprotease-9 (MMP-9) production, weak adhesion molecules E selectin, intercellular (ICAM) Adhesion Molecules (VCAM), secretion chemokines Interleukin-6 (IL-6), cyclin D-1. There no direct link between lipid metabolism anticancer activity, except for fact that actions dependent from PPARα agonism. exhibits independent activities. Conclusions:  There strong indicating can disrupt growth-related different cancers, anti-inflammatory effects. Therefore may useful a complementary adjunct treatment cancer, particularly included anti-angiogenic protocols those currently increasingly used glioblastoma. sound reasons initiate well planned phase II clinical trials cancer.