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Effects of dietary chemopreventive phytochemicals on P-glycoprotein function

Tomohiro Nabekura1, Shizu Kamiyama, Shuji Kitagawa

  • 1Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata, Japan. nabe@niigata-pharm.ac.jp

Insights

Certain dietary phytochemicals, including capsaicin and curcumin, inhibit P-glycoprotein (P-gp) function. This finding suggests potential drug-food interactions with these natural compounds.

Area of Science:

  • Pharmacology
  • Nutritional Science
  • Cancer Biology

Background:

  • P-glycoprotein (P-gp) is a key efflux transporter involved in multidrug resistance (MDR) in cancer cells.
  • Dietary phytochemicals are natural compounds found in plants with potential chemopreventive properties.
  • Understanding phytochemical interactions with P-gp is crucial for predicting drug efficacy and potential food-drug interactions.

Purpose of the Study:

  • To investigate the effects of various dietary phytochemicals on P-glycoprotein function.
  • To determine if natural chemopreventive compounds can modulate P-gp-mediated drug efflux.

Main Methods:

  • Utilized human multidrug-resistant carcinoma KB-C2 cells.
  • Employed fluorescent P-glycoprotein substrates: daunorubicin and rhodamine 123.
  • Examined the effects of capsaicin, curcumin, [6]-gingerol, resveratrol, sulforaphane, 6-methylsulfinyl hexyl isothiocyanate (6-HITC), indole-3-carbinol (I3C), diallyl sulfide, and diallyl trisulfide.

Main Results:

  • Capsaicin, curcumin, [6]-gingerol, and resveratrol increased daunorubicin accumulation in KB-C2 cells in a dose-dependent manner.
  • These phytochemicals also increased rhodamine 123 accumulation and decreased its efflux from KB-C2 cells.
  • Sulforaphane, 6-HITC, I3C, diallyl sulfide, and diallyl trisulfide showed no significant effect on P-gp function.

Conclusions:

  • Dietary phytochemicals such as capsaicin, curcumin, [6]-gingerol, and resveratrol inhibit P-glycoprotein function.
  • These findings highlight the potential for drug-food interactions involving these specific phytochemicals and P-gp substrates.
  • Further research is warranted to explore the clinical implications of these interactions in cancer therapy and drug development.

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