Multi-Target Approaches in Colon Cancer Chemoprevention Based on Systems Biology of Tumor Cell-Signaling

HMG-R inhibitors block the conversion of 3-HMG-CoA to mevalonate, preventing the formation of Farnesyl-PP and Geranylgeranyl-PP and subsequently, prenylation of Ras, Raf, Rho and lamin B. HMG-R inhibitors also block cholesterol, thereby disrupting Cav-1 associated signaling and lipid bodies. COX-2 activates β-Catenin, AKT and subsequently STAT3 and NFκB. STAT3, β-Catenin and NFκB then translocate to the nucleus and transcribe genes involved in survival and proliferation. COX-2 also promotes lipid body formation.Abbreviations: NFκB: nuclear factor κB; Cyc D1: Cyclin D1; B-Cat: β-catenin; ERK: extracellular regulated kinase; AKT: also known as protein kinase B (PKB); STAT3: signal trandsducer and activator of transcription; Cav-1: caveolin-1; EGFR: epidermal growth factor receptor; IGFR: insulin growth factor receptor; TM: transmembrane protein; LB: lipid bodies; PL: phospho lipids; AA: arachidonic acid; COX-2: cyclooxygenase 2; VEGF: vascular endothelial growth factor; iNOS: inducible nitric oxide synthase; ilk: integrin linked kinase; ROCK: Rho kinase: MEK: MAP kinase.

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Multi-Target Approaches in Colon Cancer Chemoprevention Based on Systems Biology of Tumor Cell-Signaling. (2008) Suresh Guruswamy, et al. Gene Regul Syst Bio. 2008;2:163-176. Figure: F2. All organisms Bos taurus Mus musculus Gallus gallus Homo sapiens Rattus norvegicus Ovis aries Canis lupus familiaris Xenopus laevis Drosophila melanogaster

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