Tamoxifen inhibits particulate-associated protein kinase C activity, and sensitises cultured human glioblastoma cells not to etoposide but to γ-radiation and BCNU
| Autor: | A.F Logullo, Elena Aida Bernard, A Brondani da Rocha, Dennis Ricardo August Mans, Cristiano Ruschel, Gilberto Schwartsmann, Albert Leyva, L.A Wetmore |
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| Rok vydání: | 1999 |
| Předmět: |
Cancer Research
medicine.medical_specialty Antineoplastic Agents Biology Transforming Growth Factor beta Cell surface receptor Internal medicine Tumor Cells Cultured medicine Humans Cytotoxicity Protein Kinase C Protein kinase C Etoposide Cell growth Drug Synergism Transforming growth factor beta Carmustine Immunohistochemistry Tamoxifen Endocrinology Receptors Estrogen Oncology Gamma Rays Cell culture biology.protein Cancer research Glioblastoma Cell Division medicine.drug |
| Zdroj: | European Journal of Cancer. 35:833-839 |
| ISSN: | 0959-8049 |
| DOI: | 10.1016/s0959-8049(99)00003-9 |
| Popis: | We investigated the potential mechanisms of tamoxifen cytotoxicity in the U-373, U-138, and U-87 human glioblastoma cell lines, namely interference with protein kinase C (PKC) activity, the oestrogen receptor, and/or the production of transforming growth factor beta 1 (TGF-beta 1). We further examined the effects of tamoxifen on the cytotoxicity exerted by gamma-radiation, 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), and etoposide in this cell line panel. Thus, the cells were treated for 4 days with tamoxifen, gamma-radiation, purified recombinant human TGF-beta 1 (rhTGF-beta 1), BCNU, or etoposide, either alone or at certain combinations. Cellular responses were evaluated with the sulphorhodamine B assay, as well as by multiple drug effect analysis, and related to PKC activities in particulate and cellular fractions; cellular oestrogen receptor contents; and the influence of rhTGF-beta 1 on cell growth. Tamoxifen inhibited cell proliferation as well as the phosphorylation capacity of the particulate, but not of the cytosolic fractions dose-dependently, at comparable kinetics, and at IC50 values of approximately 15 microM. At these concentrations, tamoxifen acted synergistically with gamma-radiation (4- to 6-fold) and additively with BCNU (approximately 2-fold), but did not affect etoposide cytotoxicity. The cells were negative to immunostaining for the oestrogen receptor, and rhRGF-beta 1 did not influence their growth up to 100 nm. Our data suggest that tamoxifen can sensitise cultured glioblastoma cells not to etoposide but to gamma-radiation and BCNU, possibly through interference with membrane PKC, supporting its evaluation in experimental protocols for primary malignant gliomas. |
| Databáze: | OpenAIRE |
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