| 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
|
|
WOS Category
|
AGRICULTURE, MULTIDISCIPLINARY
FOOD SCIENCE & TECHNOLOGY
CHEMISTRY, APPLIED
|
| Resource |
| DNA material |
pMDRA1 (RDB01372) |
