| RRC ID |
45319
|
| Author |
Umsumarng S, Pitchakarn P, Sastraruji K, Yodkeeree S, Ung AT, Pyne SG, Limtrakul P.
|
| Title |
Reversal of human multi-drug resistance leukaemic cells by stemofoline derivatives via inhibition of P-glycoprotein function.
|
| Journal |
Basic Clin Pharmacol Toxicol
|
| Abstract |
Our previous study reported multi-drug resistance (MDR) reversing properties of synthetic stemofoline derivatives (STFD), OH-A1, NH-B6 and NH-D6 on P-glycoprotein (P-gp) overexpressing leukaemic cells (K562/Adr); however, the mechanism was unclear. In this study, we further investigated whether the STFD reverse MDR through either the inhibition of P-gp function or expression in K562/Adr cells, or both. The P-gp functional studies showed that the STFD increased the accumulation of calcein-AM, rhodamine 123 and [(14) C]-doxorubicin in K562/Adr cells, while the effects have not been seen in their parental sensitive cancer cell line (K562). Further, the STFD did not alter the P-gp expression as determined by Western blotting. This study concludes that the STFD reverse MDR via the inhibition of P-gp function. The efficacy of the STFD to inhibit P-gp function followed the order: NH-B6 > OH-A1 > NH-D6. These compounds could be introduced as candidate molecules for treating cancers exhibiting P-gp-mediated MDR.
|
| Volume |
116(5)
|
| Pages |
390-7
|
| Published |
2015-5-1
|
| DOI |
10.1111/bcpt.12331
|
| PMID |
25265513
|
| MeSH |
ATP Binding Cassette Transporter, Subfamily B, Member 1 / antagonists & inhibitors*
ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
Antineoplastic Agents / pharmacology*
Cell Cycle Checkpoints / drug effects
Cell Survival / drug effects
Dose-Response Relationship, Drug
Drug Resistance, Multiple / drug effects*
Drug Resistance, Neoplasm / drug effects*
Heterocyclic Compounds, 4 or More Rings / pharmacology*
Heterocyclic Compounds, 4 or More Rings / toxicity
Humans
K562 Cells
Leukemia, Erythroblastic, Acute / drug therapy*
Leukemia, Erythroblastic, Acute / genetics
Leukemia, Erythroblastic, Acute / metabolism
Leukemia, Erythroblastic, Acute / pathology
|
| IF |
2.651
|
| Times Cited |
6
|
|
WOS Category
|
PHARMACOLOGY & PHARMACY
TOXICOLOGY
|
| Resource |
| Human and Animal Cells |
K562(RCB1897)
K562/Adr(RCB1898) |
