Bryostatin 1-induced modulation of nucleoside transporters and 2-chlorodeoxyadenosine influx in WSU-CLL cells
| Autor: | H H Mantsch, Frances W.J. Beck, Ayad Al-Katib, Ramzi M. Mohammad, I Ahmad, K Z Liu, Nathan R. Wall |
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| Rok vydání: | 2000 |
| Předmět: |
Male
Bryostatin 1 Biological Transport Active Down-Regulation Antineoplastic Agents Nucleoside Transport Proteins Nucleoside transporter chemistry.chemical_compound Lactones Thioinosine Deoxycytidine Kinase Genetics Chlorodeoxyadenosine Tumor Cells Cultured Humans Kinase activity Bryostatin Phosphorylation Aged biology Membrane Proteins General Medicine Dipyridamole Cell cycle Bryostatins Leukemia Lymphocytic Chronic B-Cell chemistry Cell culture Drug Resistance Neoplasm biology.protein Cancer research Cladribine Macrolides Carrier Proteins Nucleoside Vidarabine |
| DOI: | 10.3892/ijmm.5.4.341 |
| Popis: | WSU-CLL cells, a fludarabine resistant B-cell chronic lymphocytic leukemia cell line, has been shown to exhibit enhanced sensitivity to 2-chlorodeoxyadenosine (2-CdA) following 48-72 h exposure to bryostatin 1. For 2-CdA to manifest its chemotherapeutic activity, it must first enter the cell through one of several specific nucleoside transporter systems. We present data to show that bryostatin 1-induced enhanced influx of 2-CdA is in part the result of bryostatin 1-induced modulation of nucleoside transporters in WSU-CLL cells. The bi-directional equilibrative NBMPR sensitive transporters in WSU-CLL cells were significantly down-regulated 90 min post-exposure to 1-200 nM bryostatin 1. This down-regulation was evident up to 144 h. In contrast, WSU-CLL cells exhibited a transient increase in Na+-dependent concentrative 2-CdA influx from 48 to 96 h after bryostatin 1 exposure which was evident for a longer duration than that accounted for by the increase in deocycytidine kinase activity. These data may, in part, explain the enhanced efficacy of 2-CdA seen in WSU-CLL cells following 48-72 h exposure to bryostatin 1. It may raise questions as to the importance of the bi-directional transporters in determining the resistance or sensitivity of CLL cells to 2-CdA or other nucleoside analogues. |
| Databáze: | OpenAIRE |
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