Fig. 2

Tocotrienol targets multiple cell signaling pathways. Modern mono-targeted therapies include celecoxib, avastin, erbitux, enbrel, herceptin, gleevec, and avastin (inhibits COX2, EGFR, TNF, HER2, bcr-abl and VEGF, respectively) and also inhibits other targets including transcription factors, enzymes, growth factors and its receptors, kinases, and anti-apoptotic proteins. Note: Celecoxib, a non-steroidal anti-inflammatory drug that selectively inhibit COX-2; avastin (bevacizumab), monoclonal antibody against VEGF; Herceptin (Trastuzumab), humanized monoclonal antibody against HER-2; Gleevac (imatinib), a multiple tyrosine kinase inhibitor. AGP, human alpha1-acid glycoprotein; AP-1, activating protein-1; Bcl-2, B-cell lymphoma protein 2; COX-2, cyclooxygenase; DNA poly, DNA polymerase; DR, death receptor; EGFR, EGF-receptor; ER, estrogen receptor; ERK, extracellular receptor kinase; GST, glutathione-S-transferase; HER-2, human epidermal growth factor receptor-2; HIF-1α, hypoxia-inducible factor-1 alpha; IAP, inhibitory apoptosis protein; ICAM-1, intracellular adhesion molecule-1; IL, interleukin; iNOS, inducible nitric oxide synthase; JAK, janus kinase; NF-κB, nuclear factor kappa B; MMP, Matrix metalloproteinase; PKC, protein kinase C, STAT, signal transducers, and activators of transcription; VCAM-1, vascular cell adhesion molecule-1; VEGF, vascular endothelial growth factor; VEGFR, VEGF receptor; IFN-γ, interferon gamma; PF-4, Platelet factor 4; 12-LOX, 12-lipoxygenase; eNOS, endothelial nitric oxide synthase; GGT, gamma-glutamyl transpeptidase; GSTP-1, glutathione-S-transferase pi; HMGCR, 3-hydroxy-3-methylglutaryl-CoA reductase; hTERT, human telomerase reverse transcriptase; NQO1, NAD(P)H dehydrogenase, quinone1; PLA-2, phospholipase A2; TRAF-1, TNF receptor-associated factor-1; XIAP, X-linked inhibitor of apoptosis protein; c-FLIP, cellular FLICE inhibitory protein, CDK, cyclin-dependent kinase; IKK, IκB kinase; Pdk-1, phosphoinositide-dependent kinase-1; PI3K, phosphoinositide 3-kinase; C/EBP-α, CCAAT/enhancer-binding protein alpha; PPAR-γ, peroxisome proliferator-activated receptor gamma; PGE-2, prostaglandin E2; TX-B2, thromboxane B2