RRC ID 32575
Author Teng YN, Hsieh YW, Hung CC, Lin HY.
Title Demethoxycurcumin modulates human P-glycoprotein function via uncompetitive inhibition of ATPase hydrolysis activity.
Journal J Agric Food Chem
Abstract Curcuminoids are major components of Curcuma longa L., which is widely used as spice in food. This study aimed at identifying whether curcumin, demethoxycurcumin, and bisdemethoxycurcumin could modulate efflux function of human P-glycoprotein and be used as chemosensitizers in cancer treatments. Without altering P-glycoprotein expression levels and conformation, the purified curcuminoids significantly inhibited P-glycoprotein efflux function. In rhodamine 123 efflux and calcein-AM accumulation assays, demethoxycurcumin demonstrated the highest inhibition potency (inhibitory IC50 = 1.56 ± 0.13 μM) among the purified curcuminoids, as well as in the fold of reversal assays. Demethoxycurcumin inhibited P-glycoprotein-mediated ATP hydrolysis under concentrations of <1 μM and efficiently inhibited 200 μM verapamil-stimulated ATPase activity, indicating a high affinity of demethoxycurcumin for P-glycoprotein. These results suggested that demethoxycurcumin may be a potential additive natural product in combination with chemotherapeutic agents in drug-resistant cancers.
Volume 63(3)
Pages 847-55
Published 2015-1-28
DOI 10.1021/jf5042307
PMID 25594233
MeSH ATP Binding Cassette Transporter, Subfamily B, Member 1 / antagonists & inhibitors* ATP Binding Cassette Transporter, Subfamily B, Member 1 / chemistry ATP Binding Cassette Transporter, Subfamily B, Member 1 / physiology Adenosine Triphosphatases / antagonists & inhibitors* Adenosine Triphosphate / metabolism Antibiotics, Antineoplastic Antineoplastic Agents Cell Line, Tumor Curcumin / analogs & derivatives* Curcumin / pharmacology Diarylheptanoids Doxorubicin / pharmacology Drug Resistance, Multiple / drug effects Fluorescent Dyes Humans Hydrolysis Rhodamine 123
IF 4.192
Times Cited 19
DNA material pMDRA1 (RDB01372)