Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.3.44 (P-glycoprotein)
 13,344 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cytotoxic effects on HCT 116, Hep G2 and HCT 116/VCR 100-1-1 cell lines of synthetic 4'-O-alkylaloenins (2-17), 4'-O-benzylaloenin (18) and 4'-O-allylaloenin (19) were examined by MTT assay, and compared with that of aloenin (1) isolated from Aloe arborescens Mill. Var. natalensis Berger which showed no marked effect (IC50 value: > 100 microM). The cytotoxic effects of 4'-O-alkylaloenin sulfates (21-29) were also examined on the same cell lines. The introduction of a longer alkyl group at the O-4' position of 1 resulted in a higher cytotoxic action on HCT 116 and Hep G2 cells. Among 4'-O-alkylaloenins 2-17, 4'-O-tetradecylaloenin 14 was the most cytotoxic to both on HCT 116 cells (IC50 value: 5.3+/-2.3 microM) and Hep G2 cells (IC50 value: 4.0+/-0.6 microM). Also among 4'-O-alkylaloenin sulfates 21-29, 4'-O-dodecylaloenin sulfate 29 was the most cytotoxic to both on HCT 116 (IC50 value: 4.8+/-0.2 microM) and Hep G2 cells (IC50 value: 4.0+/-0.5 microM). 4'-O-Alkylaloenins 7-14 and 4'-O-alkylaloenin sulfates 24-29 were also cytotoxic to Hep G2 and HCT 116/VCR 100-1-1 cell lines, which overexpress P-glycoprotein, as well as HCT 116 cell lines which scarcely express it.
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PMID:4'-O-Alkyaloenin derivatives and their sulfates directed toward overcoming multidrug resistance in tumor cells. 1563 36

The aims of this study were to carry out a thorough quality control setup for essential Caco-2 cell characteristics in P-glycoprotein (P-gp) inhibition studies and to explore if Aloe vera juice (AVJ) inhibits the bidirectional transport of the P-gp substrate digoxin (30 nm). Seven AVJ concentrations (0.00001-1.0 mg/mL), anticipated to cover a clinically relevant range, were tested and digoxin apparent permeability coefficients (Papp), net Papp values (Papp(Net)) and net flux values (J(Net)) were calculated. Relevant validation parameters for P-gp inhibition studies in Caco-2 cells are suggested to include, as a minimum, an assay linearity test with and without a known P-gp inhibitor, cell cytotoxicity testing (MTT-test) for substrates and inhibitors, and cell integrity testing by TEER and mannitol transport measurements. The question is also raised whether a minimum effect of a reference P-gp inhibitor as verapamil should be demanded. Cell cytotoxicity was seen for digoxin at concentrations >or=3 microM and for AVJ at 10 mg/mL. AVJ did not inhibit the P-gp transport of digoxin in any of the concentrations tested. This indicates that AVJ is no inhibitor of the P-gp mediated transport of digoxin in vitro if AVJ is present in clinically relevant concentrations.
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PMID:Caco-2 cell methodology and inhibition of the P-glycoprotein transport of digoxin by Aloe vera juice. 1900 53

Folk medicine has attributed antitumor properties to preparations from Aloe vera. We have studied the effects of five purified compounds from the plant on human K562 leukemia and on its multidrug resistant (MDR) variant, K562/R. The glycosides aloin A and B, aloesin and aloeresin were devoid of antitumor activity up to 200 mu M concentrations. Only the aglycone aloe emodin produced reproducible antitumor effects, which, interestingly, were more pronounced in the MDR, P-glycoprotein overexpressing, cell line. Its IC50 was in fact 29 mu M in K562 and 10.5 mu M in K562/R. Aloe emodine caused mainly cytostasis and accumulation of the cells in the S and G(2)-M phases of the cell cycle during the first 48 h of treatment. Thereafter, massive cell death ensued. Research on the antitumor activity of compounds extracted from Aloe vera probably deserves continuation.
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PMID:Effects of highly purified anthraquinoid compounds from Aloe vera on sensitive and multidrug resistant leukemia cells. 2159 55

Aloe, the leaf juice of Aloe vera, is a popular functional food worldwide. The major constituents of aloe are polyphenolic anthranoids such as aloin, aloe-emodin and rhein. Cyclosporine (CSP), an immunosuppressant with a narrow therapeutic window, is a probe substrate of P-glycoprotein (P-gp), an efflux pump, and CYP 3A4. This study first investigated the serum kinetics of aloe, then evaluated the modulation effects of aloe on P-gp and CYP 3A through an aloe-CSP interaction study in rats. The serum kinetic study showed that aloe-emodin glucuronides (G) and rhein sulfates/glucuronides (S/G) were major molecules in the bloodstream. The aloe-CSP interaction study showed that the systemic exposure to CSP was significantly decreased by either a single dose or multiple doses of aloe. The results of in vitro studies indicated that aloe activated P-gp and aloe metabolites activated CYP 3A4. In conclusion, aloe ingestion activated the functions of P-gp and CYP 3A in rats.
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PMID:Aloe activated P-glycoprotein and CYP 3A: a study on the serum kinetics of aloe and its interaction with cyclosporine in rats. 2800 1