Phytochemicals & Metabolism in Pancreatic Diseases/Pandol, Stephen

University Of California Los Angeles, Los Angeles CA

Investigators

Linked publications & trials

Abstract

Evidence from population studies suggests that phytochemicals in fruits and vegetables provide a[unreadable] protective effect against cancer including pancreatic cancer. The majority of cancer patients besides[unreadable] traditional treatments also use natural non-prescription cancer drugs, of which, most are of plant origin.[unreadable] Therefore, the mechanistic understanding of potential benefits of phytochemicals would be of great[unreadable] importance in prevention of pancreatic cancer as well as disorders that increase the risk of pancreatic cancer[unreadable] (i.e. chronic pancreatitis) by identifying target pathways and beneficial effects of these molecules in foods[unreadable] and nutritional supplements.[unreadable] We have recently demonstrated that both growth factors and extracellular matrix proteins activate[unreadable] prosurvival pathways in pancreatic cancer cells through their ability to activate systems that generate[unreadable] reactive oxygen species (ROS). Further, we have determined that the pancreatic stellate cell, the cell[unreadable] responsible for fibrosis and inflammation in chronic pancreatitis and the desmoplastic reaction of pancreatic[unreadable] adenocarcinoma, also uses the production of ROS to mediate proliferation with growth factor stimulation.[unreadable] In preliminary data we show that selected phytochemicals (rottlerin, ellagic acid, embelin, lycopene) act to[unreadable] both attenuate the production of ROS in pancreatic cancer and stellate cells and inhibit their DMA synthesis.[unreadable] To initiate investigations into the mechanisms underlying the antiproliferative effects of these molecules we[unreadable] considered the possibility that ROS are necessary in these proliferative cells because they regulate the[unreadable] pentose cycle pathways which, in turn, are necessary for the production of ribose and deoxyribose for the[unreadable] synthesis of nucleic acids. We provide preliminary metabolomic data to support this hypothesis.[unreadable] The experiments in this project are designed to test the effect of each of rottlerin, ellagic acid, embelin,[unreadable] curcumin and lycopene on regulating the proliferative metabolic phenotype of the pancreatic stellate and[unreadable] cancer cells; and further to determine the role that their inhibition of ROS production plays in regulation of[unreadable] this phenotype. We will use this information to design experiments to test the phytochemicals for prevention[unreadable] and/or treatment of the two disorders of the exocrine pancreas involving proliferative disorders of stellate and[unreadable] cancer cells-chronic pancreatitis and pancreatic cancer using experimental animal models.