AI Article Synopsis
- The study focuses on the ABCG2 half-transporter, which is linked to resistance against certain chemotherapy drugs, including indolocarbazole derivatives, in cancer cells.
- Researchers compared two versions of ABCG2 (wild type 482R and mutant 482T) to see how they impacted cross-resistance patterns, finding both types conferred strong resistance to indolocarbazoles.
- The transport mechanism of indolocarbazole compound A was further explored, showing it was actively transported in cells and that its movement was energy-dependent, suggesting distinct binding sites and transport mechanisms for other drugs like mitoxantrone.
Article Abstract
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.
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| http://dx.doi.org/10.1016/s0006-291x(02)02712-2 | DOI Listing |
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