ABCG2 confers resistance to indolocarbazole compounds by ATP-dependent transport
| Autor: | Hiroharu Arakawa, Yoshikazu Hara, Hideya Komatani, Susumu Nishimura, Rinako Nakagawa |
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| Rok vydání: | 2002 |
| Předmět: |
Indoles
animal structures Arginine Stereochemistry Carbazoles Biophysics Antineoplastic Agents Breast Neoplasms ATP-binding cassette transporter Biology Indolocarbazole Biochemistry chemistry.chemical_compound Adenosine Triphosphate Tumor Cells Cultured ATP Binding Cassette Transporter Subfamily G Member 2 Humans Binding site Threonine Molecular Biology chemistry.chemical_classification Cell-Free System Molecular Structure Cytoplasmic Vesicles Osmolar Concentration Wild type Biological Transport Cell Biology Drug Resistance Multiple Neoplasm Proteins Amino acid chemistry embryonic structures ATP-Binding Cassette Transporters Female sense organs Mitoxantrone Nucleoside |
| Zdroj: | Biochemical and Biophysical Research Communications. 299:669-675 |
| ISSN: | 0006-291X |
| Popis: | The ABC half-transporter, ABCG2, is known to confer resistance to chemotherapeutic agents including indolocarbazole derivatives. MCF7 cells were introduced by either wild type ABCG2 (ABCG2-482R) or mutant ABCG2 (-482T), whose amino acid at position 482 is substituted to threonine from arginine, and their cross-resistance pattern was analyzed. Although this amino acid substitution seems to affect cross-resistance patterns, both 482T- and 482R-transfectants showed strong resistance to indolocarbazoles, confirming that ABCG2 confers resistance to them. For further characterization of ABCG2-mediated transport, we investigated indolocarbazole compound A (Fig. 1) excretion in cell-free system. Compound A was actively transported in membrane vesicles prepared from one of the 482T- transfectants and its uptake was supported by hydrolysis of various nucleoside triphosphates. This transport was inhibited completely by the other indolocarbazole compound, but not by mitoxantrone, implying that the binding site of mitoxantrone or the transport mechanisms for mitoxantrone is different from those of indolocarbazoles. These results showed that ABCG2 confers resistance to indolocarbazoles by transporting them in an energy-dependent manner. |
| Databáze: | OpenAIRE |
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