AI Article Synopsis

  • - The trial data suggest that individual patient differences in how their bodies absorb and break down black raspberry components affect their response to oral cancer prevention treatments.
  • - Key studies have identified anthocyanins, the compounds in black raspberries, as significant contributors to their cancer-fighting properties, with various tests confirming the presence and activity of related metabolic enzymes in human oral tissues.
  • - Analyses of saliva after using black raspberry rinses indicated that these anthocyanins can be retained and metabolized in the mouth, similar to processes in the intestines, which implies that individual variations in metabolism could influence the effectiveness of cancer preventive treatments.

Article Abstract

Our oral cancer chemoprevention trial data implied that patient-specific differences in local retention and metabolism of freeze-dried components of black raspberries (BRB) affected therapeutic responsiveness. Subsequent studies have confirmed that anthocyanins are key contributors to BRB's chemopreventive effects. Consequently, functional assays, immunoblotting, and immunohistochemical analyses to evaluate levels and distribution of BRB anthocyanin-relevant metabolic enzymes in human oral tissues were conducted. Liquid chromatography/tandem mass spectrometry (LC/MS-MS) analyses of time course saliva samples collected following BRB rinses were conducted to assess local pharmacokinetics and compare the capacities of three different BRB rinse formulations to provide sustained intraoral levels of anthocyanins. Protein profiles showed the presence of key metabolic enzymes in all 15 oral mucosal tissues evaluated, whereas immunohistochemistry confirmed these enzymes were distributed within surface oral epithelia and terminal salivary ducts. β-Glucosidase assays confirmed that whole and microflora-reduced saliva can deglycosylate BRB anthocyanins, enabling generation of the bioactive aglycone, cyanidin. LC/MS-MS analyses showed retention of parent anthocyanins and their functional, stable metabolite, protocatechuic acid, in saliva for up to 4 hours after rinsing. Furthermore, postrinse saliva samples contained glucuronidated anthocyanin conjugates, consistent with intracellular uptake and phase II conversion of BRB anthocyanins into forms amenable to local recycling. Our data show that comparable to the small intestine, the requisite hydrolytic, phase II and efflux transporting enzymes necessary for local enteric recycling are present and functional in human oral mucosa. Notably, interpatient differences in anthocyanin bioactivation and capacities for enteric recycling would impact treatment as retention of bioactivated chemopreventives at the target site would sustain therapeutic effectiveness.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3151333PMC
http://dx.doi.org/10.1158/1940-6207.CAPR-11-0040DOI Listing

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