RRC ID 54691
Author Fujita D, Arai T, Komori H, Shirasaki Y, Wakayama T, Nakanishi T, Tamai I.
Title Apple-Derived Nanoparticles Modulate Expression of Organic-Anion-Transporting Polypeptide (OATP) 2B1 in Caco-2 Cells.
Journal Mol Pharm
Abstract Interaction of foods with intestinal transporters has generally been ascribed to small molecules, but recently, edible-plant-derived nanoparticles (NPs) have been suggested to affect intestinal function. Here, we examined the effects of NPs contained in edible fruits on intestinal transporters. Apple-derived NPs (APNPs) were isolated by ultracentrifugation and characterized by measurement of particle size distribution and electron microscopy. Human epithelial colorectal adenocarcinoma (Caco-2) cells internalized fluorescently labeled APNPs, suggesting that fruit-derived NPs would be internalized into intestinal epithelial cells in vivo. We found that the mRNA expression levels of several transporters, including organic-anion-transporting polypeptide (OATP) 2B1, were changed in APNP-treated Caco-2 cells. The protein expression and activity of OATP2B1 were also decreased by APNP exposure, as determined by Western blotting and measurements of [3H]estrone-3-sulfate uptake by Caco-2 cells, respectively. These actions required intact APNPs, because sonication or boiling abrogated the effects. Since the content of apple-derived small molecules in APNPs was negligible, the observed decrease of OATP2B1 expression appears to be mediated by large molecules in the APNPs. We further found that the 3'-untranslated region of the OATP2B1 gene was required for the response to APNPs, suggesting that microRNA in the APNPs might be involved. These results propose a novel mechanism, in which large molecules such as microRNA in food could affect intestinal transporters through food-derived NPs, which also demonstrates that food-derived NPs should be useful for delivery of biologically active large molecules to intestinal tissues.
Volume 15(12)
Pages 5772-5780
Published 2018-12-3
DOI 10.1021/acs.molpharmaceut.8b00921
PMID 30359033
MeSH Caco-2 Cells Drug Carriers / administration & dosage Drug Carriers / chemistry Drug Carriers / pharmacokinetics* Fruit / chemistry* Humans Intestinal Mucosa / cytology Intestinal Mucosa / metabolism Malus / chemistry* Nanoparticles / administration & dosage Nanoparticles / chemistry Organic Anion Transporters / metabolism* Plants, Edible / chemistry*
IF 4.396
Times Cited 5
Human and Animal Cells CACO-2(RCB0988) 293(RCB1637)