Effects of Protein Kinase C Modulators on Multidrug Resistance in Human Glioma Cells
| Autor: | Katsuya Miyaji, Eiichi Tani, Ikuya Yamaura, Tsuyoshi Matsumoto, Keizo Kaba |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
Vincristine
medicine.medical_specialty Immunoblotting Down-Regulation Naphthalenes chemistry.chemical_compound Internal medicine Tumor Cells Cultured medicine Humans Polycyclic Compounds Calphostin ATP Binding Cassette Transporter Subfamily B Member 1 Phosphorylation Protein Kinase C Protein kinase C P-glycoprotein biology Glioma Molecular biology Drug Resistance Multiple Isoenzymes Endocrinology Calphostin C chemistry Cell culture Tetradecanoylphorbol Acetate biology.protein Surgery Neurology (clinical) medicine.drug |
| Zdroj: | Neurosurgery. 36:565-572 |
| ISSN: | 0148-396X |
| DOI: | 10.1227/00006123-199503000-00016 |
| Popis: | To identify the role of protein kinase C (PKC) in multidrug resistance, the effects of phorbol-12-myristate-13-acetate (PMA), a PKC activator, or calphostin C, a PKC inhibitor, on intracellular vincristine accumulation and expression of P-glycoprotein phosphorylation were studied in one multidrug-resistant and three multidrug-sensitive human glioma cell lines. Basal PKC activities and immunoreactivities of PKC-alpha and -zeta were higher in multidrug-resistant cells than in multidrug-sensitive cells. There was no significant difference in the immunoreactivity of PKC-delta between multidrug-resistant and -sensitive cells, and immunoreactive PKC-beta, -gamma, and -epsilon were not detected in either multidrug-resistant or -sensitive cells. The treatment of multidrug-resistant cells with 100 nM PMA for 2 hours resulted in the activation not of PKC-zeta but of PKC-alpha, with concomitant decrease in vincristine accumulation and increase in P-glycoprotein phosphorylation. The exposure of multidrug-resistant cells to 100 nM PMA for 24 hours induced down-regulation not of PKC-zeta but of PKC-alpha, with concurrent decrease in vincristine accumulation, and reduced but still increased P-glycoprotein phosphorylation. The treatment of multidrug-resistant cells with 100 nM calphostin C for 2 hours decreased immunoreactive PKC-zeta and not immunoreactive PKC-alpha, inducing increase in vincristine accumulation, with concomitant decrease in P-glycoprotein phosphorylation. There was no evidence of significant change in vincristine accumulation in multidrug-sensitive cells treated with PMA or calphostin C. This may suggest that at least two isozymes of PKC, PKC-alpha and -zeta, are involved in P-glycoprotein phosphorylation and that vincristine efflux function in multidrug-resistant human glioma cells is closely associated with P-glycoprotein phosphorylation and is decreased by PKC inhibitor. |
| Databáze: | OpenAIRE |
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