Effects of alkyl gallates on P-glycoprotein function.
In this study, we examined the effects of the food antioxidants, alkyl gallates, on the function of P-glycoprotein (P-gp) and elucidated the importance of alkyl chains and gallic acid moieties on the activity of P-gp. We examined the effects of three alkyl (n-butyl, n-octyl and n-dodecyl) gallates and their related compounds on the cellular accumulation and efflux of rhodamine 123 and daunorubicin in P-gp overexpressing KB-C2 cells. Alkyl gallates increased the cellular accumulation of these P-gp substrates dependent on their alkyl chain lengths by inhibiting the efflux of the substrates. n-Dodecylresorcinol also increased the accumulation, but its effect was less than that of n-dodecyl gallate. However, either lauric acid or n-dodecyl-beta-d-maltoside, which does not have a phenol group, did not increase the accumulation. The results indicated that both the gallic acid moiety and a long alkyl chain play important roles in the modification of P-gp function. The cytotoxicity of daunorubicin was recovered in the presence of alkyl gallates possibly due to their inhibition of P-gp function.
Kitagawa
Shuji
S
Laboratory of Pharmaceutics, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Japan. kitagawa@niigata-pharm.ac.jp
Nabekura
Tomohiro
T
Kamiyama
Shizu
S
Takahashi
Tomoharu
T
Nakamura
Yutaka
Y
Kashiwada
Yoshiki
Y
Ikeshiro
Yasumasa
Y
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D003630:Daunorubicin / Q000494:pharmacology; D005707:Gallic Acid / Q000494:pharmacology*; D021381:Protein Transport
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D005707:Gallic Acid; D003630:Daunorubicin