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MRP1-dependent Collateral Sensitivity of Multidrug-resistant Cancer Cells: Identifying Selective Modulators Inducing Cellular Glutathione Depletion
- Source :
- Current Medicinal Chemistry, Current Medicinal Chemistry, Bentham Science Publishers, 2017, 24 (12), ⟨10.2174/0929867324666161118130238⟩
- Publication Year :
- 2017
- Publisher :
- HAL CCSD, 2017.
-
Abstract
- Cancer cells are permanently being selected for survival and proliferation. During this process, tumor cells often co-opt basic physiological mechanisms to protect themselves from toxic chemotherapy. One of these mechanisms is the overexpression of ATP-binding cassette (ABC) drug efflux pumps leading to multidrug resistance (MDR) of cancer cells through an increase of drug efflux. In the past 20 years, many efforts were done to circumvent MDR through the inhibition of ABC transporters. A number of inhibitors of these transporters were found but are rarely specific or rationally developed. Beside this approach, a new therapeutic strategy towards eradicating drug resistant tumor cells has recently emerged from the observation that cancer cells expressing a high level of these pumps show an unexpected hypersensitivity, called collateral sensitivity (CS) to a selected subset of chemical compounds. In this review, we target the multidrug resistance protein 1 (MRP1) and after a non-exhaustively highlighting of some of the most exemplary inhibitors of MRP1 and modulators of its expression, we focus on CS agents specifically targeting MRP1 which becomes, when overexpressed, the so calledquot;Achilles#039; heelquot; of multidrug resistant cancer cells. We discuss the link between the prominent role of glutathione translocation and related redox balance of the cell and the CS induced by certain types of compounds. The latter are discussed according to their chemical class, and perspectives in their development for successful eradication of resistant cancer are proposed.
- Subjects :
- 0301 basic medicine
Drug
media_common.quotation_subject
Cell
ATP-binding cassette transporter
Antineoplastic Agents
[SDV.CAN]Life Sciences [q-bio]/Cancer
Drug resistance
Pharmacology
Biology
Biochemistry
03 medical and health sciences
Multidrug Resistance Protein 1
Neoplasms
Drug Discovery
medicine
Animals
Humans
ATP Binding Cassette Transporter, Subfamily B, Member 1
[SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM]
ComputingMilieux_MISCELLANEOUS
media_common
Molecular Structure
Organic Chemistry
Glutathione
Drug Resistance, Multiple
3. Good health
Multiple drug resistance
030104 developmental biology
medicine.anatomical_structure
Drug Resistance, Neoplasm
Cancer cell
Molecular Medicine
Efflux
Subjects
Details
- Language :
- English
- ISSN :
- 09298673
- Database :
- OpenAIRE
- Journal :
- Current Medicinal Chemistry, Current Medicinal Chemistry, Bentham Science Publishers, 2017, 24 (12), ⟨10.2174/0929867324666161118130238⟩
- Accession number :
- edsair.doi.dedup.....c226004dfef337a683dea415e479aa5a