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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
Abstract:
The effects of dietary phytochemicals on P-glycoprotein function were investigated using human multidrug-resistant carcinoma KB-C2 cells and the fluorescent P-glycoprotein substrates daunorubicin and rhodamine 123. The effects of natural chemopreventive compounds, capsaicin found in chilli peppers, curcumin in turmeric, [6]-gingerol in ginger, resveratrol in grapes, sulforaphane in broccoli, 6-methylsulfinyl hexyl isothiocyanate (6-HITC) in Japanese horseradish wasabi, indole-3-carbinol (I3C) in cabbage, and diallyl sulfide and diallyl trisulfide in garlic, were examined. The accumulation of daunorubicin in KB-C2 cells increased in the presence of capsaicin, curcumin, [6]-gingerol, and resveratrol in a concentration-dependent manner. The accumulation of rhodamine 123 in KB-C2 cells was also increased, and the efflux of rhodamine 123 from KB-C2 cells was decreased by these phytochemicals. Sulforaphane, 6-HITC, I3C, and diallyl sulfide and diallyl trisulfide had no effect. These results suggest that dietary phytochemicals, such as capsaicin, curcumin, [6]-gingerol, and resveratrol, have inhibitory effects on P-glycoprotein and potencies to cause drug-food interactions.
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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