| Title |
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en
Schedule-Dependent Cytotoxicity of Etoposide and Cyclophosphamide in P-Glycoprotein-Expressing Human Leukemic K-562 Cells
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| Creator |
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| Accessrights |
open access |
| Subject |
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Other
en
etoposide
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Other
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P-glycoprotein
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Other
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schedule
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Other
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cyclophosphamide
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Other
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cell cycle
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NDC
499
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| Description |
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Abstract
en
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.
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| Publisher |
en
Pharmaceutical Society of Japan
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| Date |
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| Language |
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| Resource Type |
journal article |
| Version Type |
VoR |
| Identifier |
HDL
http://hdl.handle.net/2115/57262
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| Relation |
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isIdenticalTo
DOI
https://doi.org/10.1248/bpb.b14-00207
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| Journal |
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Biological & Pharmaceutical Bulletin
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Volume Number37
Issue Number8
Page Start1323
Page End1329
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| File |
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| Oaidate |
2023-07-26 |
