We examined chemo-preventive mechanisms of apiaceous vegetable intake against 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Rats fed either a purified diet, or purified diet supplemented with 21% apiaceous vegetables (API), were injected with PhIP after 6 d of feeding and colons harvested 24 h later. There was a trend for increased colonic mRNA expression of P-glycoprotein, a PhIP efflux transporter. No DNA damage response genes were up-regulated by API but 13 of these genes were down-regulated, compared to the positive control group, which may have been due to formation of fewer PhIP-DNA adducts. In colonic miRNA profiling, 11 out of 421 miRNAs were modulated in the API group, 3 of which target 19 mRNAs involved in cancer signaling pathways. API increased miR-19a, which targets Ccnd1, a potential oncogene responsible for G1-S cell cycle progression. In conclusion, apiaceous vegetable intake may be chemopreventive through modification of miRNA expression as well as P-glycoprotein expression in colon.
Bibliographical noteFunding Information:
This work was supported by the Masonic Cancer Center, University of Minnesota . S.P.T. and D.D.G. designed the research; J.K.K. and S.P.T. conducted the research and analyzed the data; J.K.K., D.D.G., and S.P.T. drafted the manuscript and approved the final content. We would like to thank Dr. Xiaoli Chen and the University of Minnesota Genomics Center for expert guidance and resources. The authors have no conflicts of interest to disclose. Appendix A
© 2018 Elsevier Ltd
- Apiaceous vegetables