Modulation of p-glycoprotein and breast cancer resistance protein by some prescribed corticosteroids.
Efflux transporters, p-glycoprotein and breast cancer resistance protein (BCRP), located at barrier sites such as the blood-brain barrier may affect distribution of steroids used for treating chronic inflammatory conditions and thus the extent to which they may perturb the hypothalamic-pituitary-adrenal axis. In the present study, six different glucocorticoids were investigated for their possible interactions with these efflux transporters. Beclomethasone dipropionate, mometasone furoate and ciclesonide active principle but not fluticasone propionate or triamcinolone, (all at 0.1 to 10 microM) caused inhibition of efflux, resulting in increased accumulation of mitoxantrone in BCRP-expressing MCF7/MR breast cancer cells and of calcein in p-glycoprotein-expressing SW620/R colon carcinoma cell. At 5 microM the same three increased sensitivity of p-glycoprotein-expressing SW620/R to doxorubicin and stimulated ATPase activity associated with BCRP expressed in bacterial membrane vesicles. Budesonide also stimulated ATPase activity. These data demonstrate the capacity of some clinically used glucocorticoids to interact with efflux transporters.
Cooray
Hiran C
HC
Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, UK.
Shahi
Sanjay
S
Cahn
Anthony P
AP
van Veen
Hendrik W
HW
Hladky
Stephen B
SB
Barrand
Margery A
MA
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000305:Adrenal Cortex Hormones / Q000494:pharmacology*; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D001507:Beclomethasone / Q000494:pharmacology; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology; D004357:Drug Synergism; D005452:Fluoresceins / Q000378:metabolism; D006801:Humans; D008942:Mitoxantrone / Q000378:metabolism; D000068656:Mometasone Furoate; D009363:Neoplasm Proteins / Q000378:metabolism*; D011244:Pregnadienediols / Q000494:pharmacology; D011282:Pregnenediones / Q000494:pharmacology
C116614:ABCG2 protein, human; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000305:Adrenal Cortex Hormones; D000903:Antibiotics, Antineoplastic; D005452:Fluoresceins; D009363:Neoplasm Proteins; D011244:Pregnadienediols; D011282:Pregnenediones; D000068656:Mometasone Furoate; D004317:Doxorubicin; D008942:Mitoxantrone; D000251:Adenosine Triphosphatases; D001507:Beclomethasone; C120481:ciclesonide; C007740:fluorexon