التفاصيل البيبلوغرافية
| العنوان: |
Mechanistic Insights into Photodynamic Regulation of Adenosine 5′-Triphosphate-Binding Cassette Drug Transporters |
| المؤلفون: |
Barry J. Liang (11437677), Sabrina Lusvarghi (2329267), Suresh V. Ambudkar (223101), Huang-Chiao Huang (1967338) |
| سنة النشر: |
2021 |
| المجموعة: |
Smithsonian Institution: Digital Repository |
| مصطلحات موضوعية: |
Biophysics, Biochemistry, Medicine, Genetics, Molecular Biology, Pharmacology, Biotechnology, Developmental Biology, Cancer, Mental Health, Hematology, Infectious Diseases, Computational Biology, Chemical Sciences not elsewhere classified, Information Systems not elsewhere classified, western blotting revealed, toxic modulators suggest, photosensitizer benzoporphyrin derivative, maximal inhibitory concentrations, new optical tools, activated bpd induces, drug transporters abcb1, abc drug transporters, optical dose, new strategies, study concerning, silico <, photodynamic therapy, photodynamic regulation, photodynamic manipulation |
| الوصف: |
Efforts to overcome cancer multidrug resistance through inhibition of the adenosine triphosphate-binding cassette (ABC) drug transporters ABCB1 and ABCG2 have largely failed in the clinic. The challenges faced during the development of non-toxic modulators suggest a need for a conceptual shift to new strategies for the inhibition of ABC drug transporters. Here, we reveal the fundamental mechanisms by which photodynamic therapy (PDT) can be exploited to manipulate the function and integrity of ABC drug transporters. PDT is a clinically relevant, photochemistry-based tool that involves the light activation of photosensitizers to generate reactive oxygen species. ATPase activity and in silico molecular docking analyses show that the photosensitizer benzoporphyrin derivative (BPD) binds to ABCB1 and ABCG2 with micromolar half-maximal inhibitory concentrations in the absence of light. Light activation of BPD generates singlet oxygen to further reduce the ATPase activity of ABCB1 and ABCG2 by up to 12-fold in an optical dose-dependent manner. Gel electrophoresis and Western blotting revealed that light-activated BPD induces the aggregation of these transporters by covalent cross-linking. We provide a proof of principle that PDT affects the function of ABCB1 and ABCG2 by modulating the ATPase activity and protein integrity of these transporters. Insights gained from this study concerning the photodynamic manipulation of ABC drug transporters could aid in the development and application of new optical tools to overcome the multidrug resistance that often develops after cancer chemotherapy. |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
unknown |
| العلاقة: |
https://figshare.com/articles/journal_contribution/Mechanistic_Insights_into_Photodynamic_Regulation_of_Adenosine_5_-Triphosphate-Binding_Cassette_Drug_Transporters/16624815Test |
| DOI: |
10.1021/acsptsci.1c00138.s001 |
| الإتاحة: |
https://doi.org/10.1021/acsptsci.1c00138.s001Test |
| حقوق: |
CC BY-NC 4.0 |
| رقم الانضمام: |
edsbas.8B590420 |
| قاعدة البيانات: |
BASE |
