Demethoxycurcumin modulates human P-glycoprotein function via uncompetitive inhibition of ATPase hydrolysis activity.

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.
Authors	Yu-Ning Teng, Yow-Wen Hsieh, Chin-Chuan Hung, Hui-Yi Lin
Journal	Journal of agricultural and food chemistry (J Agric Food Chem) Vol. 63 Issue 3 Pg. 847-55 (Jan 28 2015) ISSN: 1520-5118 [Electronic] United States
PMID	25594233 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	ATP Binding Cassette Transporter, Subfamily B, Member 1 Antibiotics, Antineoplastic Antineoplastic Agents Diarylheptanoids Fluorescent Dyes Rhodamine 123 Doxorubicin Adenosine Triphosphate Adenosine Triphosphatases Curcumin demethoxycurcumin
Topics	ATP Binding Cassette Transporter, Subfamily B, Member 1 (antagonists & inhibitors, chemistry, physiology) Adenosine Triphosphatases (antagonists & inhibitors) Adenosine Triphosphate (metabolism) Antibiotics, Antineoplastic Antineoplastic Agents Cell Line, Tumor Curcumin (analogs & derivatives, pharmacology) Diarylheptanoids Doxorubicin (pharmacology) Drug Resistance, Multiple (drug effects) Fluorescent Dyes Humans Hydrolysis Rhodamine 123

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