| RRC ID |
64183
|
| Author |
Tazawa Y, Usukubo I, Takada K, Takekuma Y, Shibayama Y, Sugawara M.
|
| Title |
Schedule-dependent cytotoxicity of Etoposide and cyclophosphamide in P-glycoprotein-expressing human leukemic K-562 cells.
|
| Journal |
Biol Pharm Bull
|
| Abstract |
Combination chemotherapy is often used to treat cancer. Many studies have shown schedule-dependent effects between anticancer drugs. Our previous studies showed that K-562 cells pretreated with non-cytotoxic concentrations of 4-hydroperoxycyclophosphamide (4-HPC), which is a preactivated analog of cyclophosphamide (CY), enhanced the cytotoxicity of etoposide (VP-16). The appearance of cellular resistance to anticancer drugs is a major problem in cancer chemotherapy. P-Glycoprotein (P-gp) plays an important role in drug resistance, and VP-16 is a substrate for this efflux pump. In the present study, we demonstrated schedule-dependent cytotoxicity of VP-16 and CY in P-gp-overexpressed K-562/P-gp cells. Cytotoxicity of VP-16 was enhanced in K-562/P-gp cells that were pretreated with a non-cytotoxic concentration of 4-HPC compared to that of cells not treated with 4-HPC. 4-HPC arrested the cell cycle at S phase. Cells in S phase are most sensitive to VP-16. The results suggest that cell cycle arrest by 4-HPC pretreatment may be responsible for the enhanced cytotoxicity of VP-16. The findings in this study should lead to improvements in clinical combination chemotherapy.
|
| Volume |
37(8)
|
| Pages |
1323-9
|
| Published |
2014-1-1
|
| DOI |
10.1248/bpb.b14-00207
|
| PII |
DN/JST.JSTAGE/bpb/b14-00207
|
| PMID |
25087953
|
| MeSH |
ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
Antineoplastic Agents / administration & dosage*
Biological Transport / drug effects
Cell Cycle / drug effects
Cell Survival / drug effects
Cyclophosphamide / administration & dosage
Cyclophosphamide / analogs & derivatives*
Drug Administration Schedule
Etoposide / administration & dosage*
Humans
K562 Cells
Leukemia / drug therapy
Leukemia / metabolism
|
| IF |
1.863
|
| Resource |
| Human and Animal Cells |
K-562(RCB1635) |
