(P26-045-25) Do Sorghum bicolor Extracts Affect Expression or Activity of Benzo[a]pyrene-Metabolizing Enzymes?

Objectives: The aromatic hydrocarbon benzo[a]pyrene (BaP) is a ubiquitous carcinogen associated with an increased risk of cancers such as colorectal cancer. BaP is metabolically activated by Phase I enzymes, including cytochrome P450 (CYP) isoforms as well as epoxide hydrolases. These modifications allow for biotransformation of BaP into more hydrophilic metabolites, facilitating their export but also increasing their potential to bind to DNA. However, diets rich in polyphenols may prevent BaP's metabolic activation by interfering with Phase I metabolism or by increasing Phase II enzymes, which inactivate BaP-metabolites. The objective of this study is to determine the extent to which extracts from two novel varietals from leaves or bran of Sorghum bicolor containing high amounts of polyphenols affect expression and activity of Phase I and Phase II enzymes in human colon cancer cells.

Methods: Simultaneous with exposure to 2.5µM BaP, human colon cancer Caco2 cells were treated with extracts from high- or low-polyphenol Sorghum (1µl/mL) or 5µM of the green tea polyphenol epigallocatechin-3-gallate (EGCG) for 6h. All control and experimental groups were statistically compared to cells treated with BaP alone.

Results: BaP increased mRNA expression of CYP1A1, CYP1A2, and CYP1B1 8-12-fold, respectively, as expected. Interestingly, mRNA expression of epoxide hydrolase 1 (EPHX1) and the Phase II enzyme, glutathione S-transferase P1, was unaffected. Our preliminary results suggest that the concentrations and/or treatment duration of the sorghum extracts were not sufficient to counteract the BaP-induced upregulation of CYP mRNA expression in Caco2 cells. However, BaP-induced CYP catalytic activity was reduced by one of the high-polyphenol sorghum extracts.

Conclusions: While mRNA expression of several Phase I/II enzymes were unaffected by a polyphenol-rich Sorghum extract, chemopreventive effects may still occur through downstream regulation of protein expression and catalytic activity. We continue to investigate the effect of Sorghum extracts on Phase I/II protein expression and activity.

Funding Sources: This study was supported by USDA ARS Kansas and Towson University.