| RRC ID |
39000
|
| 著者 |
Nakatsu S, Kondo S, Kondo Y, Yin D, Peterson JW, Kaakaji R, Morimura T, Kikuchi H, Takeuchi J, Barnett GH.
|
| タイトル |
Induction of apoptosis in multi-drug resistant (MDR) human glioblastoma cells by SN-38, a metabolite of the camptothecin derivative CPT-11.
|
| ジャーナル |
Cancer Chemother Pharmacol
|
| Abstract |
The overexpression of the multidrug resistance (mdr1) gene and its product, P-glycoprotein (P-gp), is thought to limit the successful chemotherapy of human tumors. Recent studies demonstrate that SN-38, a metabolite of the camptothecin (CPT) derivative CPT-11, has antitumor effects on several tumors, but the mechanisms responsible for its cytotoxicity remain unclear. We therefore determined whether SN-38 has cytotoxic effects on MDR human glioblastoma GB-1 cells and non-MDR human glioblastoma U87-MG cells. Furthermore, we determined what role SN-38 plays in the induction of cytotoxicity in these tumor cells. In this study, we demonstrated that SN-38 had significantly stronger antitumor effects on GB-1 and U-87MG cells than did CPT (P < 0.01 and P < 0.05, respectively). In addition, findings obtained using a DNA fragmentation assay, Hoechst 33258 staining, in situ end-labeling and cell cycle analysis demonstrated that SN-38 induced apoptosis in these tumors. Our results suggest that SN-38 has a stronger antitumor effect on malignant glioma cells regardless of MDR expression than does CPT, and therefore can be considered a new chemotherapeutic agent potentially effective in the treatment of human primary or recurrent malignant gliomas resistant to chemotherapy.
|
| 巻・号 |
39(5)
|
| ページ |
417-23
|
| 公開日 |
1997-1-1
|
| DOI |
10.1007/s002800050592
|
| PMID |
9054955
|
| MeSH |
Antineoplastic Agents, Phytogenic / toxicity
Apoptosis / drug effects*
Camptothecin / analogs & derivatives*
Camptothecin / toxicity
Cell Cycle / drug effects
Cell Line
Cell Survival / drug effects*
DNA, Neoplasm / drug effects
Dose-Response Relationship, Drug
Drug Resistance, Multiple*
Flow Cytometry
Glioblastoma
Humans
Irinotecan
Kinetics
Tumor Cells, Cultured
|
| IF |
2.967
|
| 引用数 |
45
|
|
WOS 分野
|
PHARMACOLOGY & PHARMACY
ONCOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
U-87 MG(RCB0419) |
