Abstract
The drug transporter ABCB1 plays a major role in drug resistance and chemotherapy failure in the treatment of breast cancer. Jadomycins are natural products synthesized by the bacteria S. venezuelae ISP5230 and inhibit the mitotic regulatory protein aurora‐B kinase. The object of our study was to investigate the cytotoxicity of jadomycins towards breast cancer cells. By MTT assay we found that Jadomycin B, DT and G were selectively toxic against MCF7 and T47D breast cancer cells compared to control human kidney (HK2) cells. Jadomycin B, DT and G did not activate ABCB1‐ATPase activity in isolated membrane preparations, suggesting that these molecules may evade the ABCB1 drug resistance transporter. In support of this, Jadomycin B and DT displayed similar cytotoxicity in MCF7 control and taxol resistant MCF7tx400 cells that overexpress ABCB1. Comparatively, MCF7tx400 cells were relatively resistant to the cytotoxic effects of the ABCB1 substrates taxol and etoposide. We conclude that Jadomycin B and DT possess effective chemotherapeutic action against both drug‐sensitive and ABCB1‐expressing drug‐resistant breast cancer cells in culture. This work was supported by the CBCF‐Atlantic chapter.
Published Version
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