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Molecular targets of (-)-epigallocatechin-3-gallate (EGCG): specificity and interaction with membrane lipid rafts Patra SK; Rizzi F; Silva A; Rugina DO; Bettuzzi SJ Physiol Pharmacol 2008[Dec]; 59 Suppl 9 (ä): 217-35Proteomic studies on anticancer activity of Green Tea Catechins (specifically EGCG) are suggesting a large set of protein targets that may directly interact with EGCG and alter the physiology of diseased cells, including cancer. Of notice, benign cells are usually left untouched. Lipid rafts have been recently recognized as signal processing hubs and suggested to be involved in drug uptake by means of endocytosis. These findings are suggesting new insights on the molecular mechanisms of anticancer drugs action. In the membrane, EGCG is hijacked by the laminin receptor (LamR), a lipid raft protein. Similar to aplidin and edelfosin, EGCG alters membrane domains composition also preventing EGF binding to EGFR, imerization of EGFR and relocation of phosphorylated EGFR to lipid rafts. In vitro studies have recently shown that EGCG also binds both DNA and RNA in GpC-rich regions. This event may importantly affect genes function. Moreover, EGCG was shown to inhibit telomerase, topoisomerase II and DNA methyltransferase 1 (DNMT1), thus ultimately affecting chromatin maintenance and remodeling. But another important alternative pathway besides interaction with specific proteins may play an important role in EGCG action: direct targeting of bioactive membrane platforms, lipid rafts. Structural alteration of the platforms deeply impact (and often inactivates) important pathways involving MAP kinases. The key issue is that, important and specific differences in lipid rafts composition have been found in transformed versus benign cells and apoptotic versus non-apoptotic cells. We suggest here that the anticancer activity of Green Tea Catechins against different kind of cancers may find an explanation in direct targeting of lipid rafts by EGCG.|Animals[MESH]|Antineoplastic Agents/isolation & purification/*pharmacology[MESH]|Apoptosis/drug effects[MESH]|Camellia sinensis/chemistry[MESH]|Catechin/*analogs & derivatives/isolation & purification/metabolism[MESH]|Drug Delivery Systems[MESH]|Humans[MESH]|Membrane Microdomains/*drug effects/metabolism[MESH]|Mitogen-Activated Protein Kinases/metabolism[MESH]|Neoplasms/drug therapy/physiopathology[MESH]|Tea/chemistry[MESH] |
