Abstract
G A A b st ra ct s of curcumin is thought to be through the inhibition of Cytochrome P450 dependent enzymes, which convert pro-mutagens to mutagens. It is critical to understand the impact of these risk factors at the molecular level so that suitable preventive strategies can be developed. Objective: Here, we investigated effects of B[a]P and Curcumin on CYP450 genes in a normal esophageal squamous epithelial cell line (HET-1A), and in an hTERT immortalized benign Barrett's cells (BAR-T). Methods: BAR-T cells were exposed for 5 minutes daily to 200uM glycochenodeoxycholic acid with an adjusted culture medium of pH 4 for 18 weeks, and untreated HET-1A cells were also used in parallel. We treated both cell types with 15, 25, 30uM B[a]P for 48hrs. Curcumin was added 30 minutes prior to adding B[a]P at a concentration of 1.5, and 3uM. AhR, CYP1A1, CYP1B1 transcripts were assessed by Real time RT-PCR analyses. Expression of target mRNA was normalized with respect to Actin Using the DeltaDelta Ct method. Results: Results show a dose dependent induction of the AhR gene on the HET-1A and BAR-T cell line by B[a]P after 48 hours of exposure. CYP1A1 and CYP1B1 genes reach maximum induction at 30uM of B[a]P. Interestingly, when Curcumin was added to the cell lines exposed to 25uM B[a]P there is a dose dependent decrease on CYP1A1 y CYP1B1 genes. (Table 1) Conclusion: Benzo[a]pyrene induces Cytochrome P450 genes in both squamous and Barrett's cells. However Barrett's cells seem more susceptible to mutagenic effects of B[a]P. Curcumin is capable of reversing mutagenic effects of B[a]P in both cell types and thus promises to be a naturally occurring compound for esophageal chemoprevention specifically in patients with a history of smoking. The study also provides an important clue in the pathogenesis of esophageal cancer.
Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
