Effects of dietary chemopreventive phytochemicals on P-glycoprotein function.
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.
Nabekura
Tomohiro
T
Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata, Japan. nabe@niigata-pharm.ac.jp
Kamiyama
Shizu
S
Kitagawa
Shuji
S
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000187:drug effects / Q000378:metabolism*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D002396:Catechols; D018890:Chemoprevention; D003474:Curcumin / Q000031:analogs & derivatives / Q000494:pharmacology; D004032:Diet; D004305:Dose-Response Relationship, Drug; D005233:Fatty Alcohols / Q000494:pharmacology; D006801:Humans; D007624:KB Cells / Q000187:drug effects / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D000077185:Resveratrol; D020112:Rhodamine 123 / Q000494:pharmacology; D013267:Stilbenes / Q000494:pharmacology; D014747:Vinblastine / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000972:Antineoplastic Agents, Phytogenic; D002396:Catechols; D005233:Fatty Alcohols; D010936:Plant Extracts; D013267:Stilbenes; D020112:Rhodamine 123; D014747:Vinblastine; C007845:gingerol; D003474:Curcumin; D000077185:Resveratrol; D002211:Capsaicin