Chemoprevention Study of Botanical Dietary Supplements by Mass Spectrometry

Botanical dietary supplements have the potential to maintain and or even improve health. In particular, some botanical dietary supplements have the potential to prevent cancer. The iTRAQ quantitative proteomics approach described in this dissertation illustrates how lycopene exerts multiple chemoprotective effects on normal human prostatic epithelial cells which are probably the origin of most prostatic adenocarcinomas. Several proteins were up or down-regulated by lycopene in directions that are consistent with reduction of oxidative stress in these cells. Lycopene was found to inhibit proliferation of prostate epithelial cells by down regulating the AKT/mTOR pathway and by up regulating genes that have growth inhibitory effects. Lycopene was shown to induce caspase dependant apoptosis and down regulate several proteins involved in anti-apoptosis process. Lycopene was also found to alter several signaling pathways including decreased androgen receptor signaling by down regulating protein DJ 1 and HSP90; enhance TNFα signaling induced apoptosis by down regulating TXNDC17; deactivating MAPK pathway and reducing inflammation by down regulating MIF; and down regulation of the AKT/mTOR pathway to slow down cell proliferation and induce apoptosis. Humulus lupulus L. (hops) is well-known as a raw material in the brewing industry to give beer the signature aroma and flavor. In recent years prenylated flavonoids in hops attracted major attention because of their diverse activities. Xanthohumol, the most abundant chalcone from hops, emerged as a potential chemoprevention agent because of its broad activities against different cancer cell lines. However, little is known about the safety of whether xanthohumol or hops extract will cause drug-herb interactions in the human body. we evaluated a hop standardized extract for possible induction of human metabolizing enzymes cytochrome P450 1A2 and 3A4. We found that the hop extract will not induce either enzyme or its corresponding mRNA level at average physiological plasma concentrations. We further evaluated the inhibition potential of the hop extract or xanthohumol in combination with other major prenylated flavonoids on drug metabolizing enzymes. Our results indicate that xanthohumol or hop extract could inhibit cytochrome P450 2C family enzymes which may affect the efficacy and safety of some CYP 2C substrate drugs when co-administere.