| RRC ID |
44268
|
| 著者 |
Umsumarng S, Pintha K, Pitchakarn P, Sastraruji K, Sastraruji T, Ung AT, Jatisatienr A, Pyne SG, Limtrakul P.
|
| タイトル |
Inhibition of P-glycoprotein mediated multidrug resistance by stemofoline derivatives.
|
| ジャーナル |
Chem Pharm Bull (Tokyo)
|
| Abstract |
Resistance to chemotherapy in cancer patients has been correlated to the overexpression of the ATP-binding cassette (ABC) drug transporters including P-glycoprotein (P-gp) that actively efflux chemotherapeutic drugs from cancer cells. We examined the multidrug resistance reversing property of stemofoline derivatives in drug-resistance human cervical carcinoma (KB-V1) and human leukemic (K562/Adr) cell lines that overexpress P-gp. Didehydrostemofoline and eleven of its derivatives were synthesized and the cytotoxicity and their effect on doxorubicin, vinblastine and paclitaxel sensitivity in drug resistant (KB-V1 and K562/Adr) and drug sensitive (KB-3-1 and K562) cell lines by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay were determined. We found that three out of the twelve stemofoline derivatives including OH-A1, NH-B6 and NH-D6 showed commitment efficiency to increase sensitivity to doxorubicin, vinblastine and paclitaxel in KB-V1 cells and increase sensitivity to doxorubicin, and paclitaxel in K562/Adr cells whereas the effects have not been seen in their parental sensitive cancer cell lines (KB-3-1 and K562). These results indicate that stemofoline derivatives reversed P-gp-mediated multidrug resistance in vitro, and thus could be developed as effective chemosensitizers to treat multidrug-resistant cancers. The molecular mechanism of modulation of P-gp would be further determined.
|
| 巻・号 |
61(4)
|
| ページ |
399-404
|
| 公開日 |
2013-1-1
|
| DOI |
10.1248/cpb.c12-00967
|
| PII |
DN/JST.JSTAGE/cpb/c12-00967
|
| PMID |
23358236
|
| MeSH |
ATP Binding Cassette Transporter, Subfamily B, Member 1 / antagonists & inhibitors*
ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
Antineoplastic Agents / toxicity
Cell Line, Tumor
Cell Survival / drug effects
Doxorubicin / toxicity
Drug Resistance, Neoplasm / drug effects
Heterocyclic Compounds, 4 or More Rings / chemical synthesis
Heterocyclic Compounds, 4 or More Rings / chemistry*
Heterocyclic Compounds, 4 or More Rings / toxicity
Humans
K562 Cells
Paclitaxel / toxicity
Vinblastine / toxicity
|
| IF |
1.416
|
| 引用数 |
14
|
|
WOS 分野
|
PHARMACOLOGY & PHARMACY
CHEMISTRY, MULTIDISCIPLINARY
CHEMISTRY, MEDICINAL
|
| リソース情報 |
| ヒト・動物細胞 |
K562/Adr(RCB1898) |
