The positive inotropic agent DPI-201106 selectively reverses ABCB1-mediated multidrug resistance in cancer cell lines
| Autor: | Megumi Murakami, Tai-Ho Hung, Suresh V. Ambudkar, Chung-Pu Wu, Sung-Han Hsiao, Ni Yeh, Yan-Qing Li, Yu-Shan Wu |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Drug Cancer Research ATP Binding Cassette Transporter Subfamily B Cardiotonic Agents Cell Survival medicine.medical_treatment media_common.quotation_subject Antineoplastic Agents Apoptosis Article Piperazines Mice 03 medical and health sciences 0302 clinical medicine Cell Line Tumor Neoplasms medicine Animals Humans Inotropic agent media_common Chemotherapy business.industry Sodium channel Drug Repositioning Drug Resistance Multiple Multiple drug resistance HEK293 Cells 030104 developmental biology Oncology Docking (molecular) 030220 oncology & carcinogenesis Cancer cell NIH 3T3 Cells Cancer research Efflux business |
| Zdroj: | Cancer Letters. 434:81-90 |
| ISSN: | 0304-3835 |
| DOI: | 10.1016/j.canlet.2018.07.022 |
| Popis: | The overexpression of ABCB1 in cancer cells is a major factor contributing to the development of multidrug resistance (MDR) and treatment failure in cancer patients. Therefore, re-sensitization of MDR cancer cells to anticancer drugs remains an important aspect in chemotherapy. The progress in developing clinically applicable synthetic inhibitors of ABCB1 has been slow, mostly due to complications associated with intrinsic toxicities and unforeseen drug-drug interactions. Here, we explored the drug-repositioning approach for cancer therapy by targeting ABCB1-mediated MDR in human cancer cells. We found that DPI-201106, a positive inotropic agent, selectively inhibits the drug efflux function of ABCB1, and in doing so, re-sensitizes ABCB1-overexpressing MDR cancer cells to conventional anticancer drugs. Furthermore, the ATPase activity of ABCB1 and docking analysis of DPI-201106 in the drug-binding pocket of ABCB1 were determined to confirm the interaction between DPI-201106 and ABCB1 protein. In summary, we revealed an additional action and a potential clinical application of DPI-201106 to reverse ABCB1-mediated MDR in human cancer cells, which may be beneficial for cancer patients who have developed multidrug resistance and no longer respond to conventional chemotherapy, and should be further investigated. |
| Databáze: | OpenAIRE |
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