2024-03-28T16:10:28Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1291402021-06-10T11:31:55Zcom_10261_128com_10261_1col_10261_381
Yeast as a biosensor of detoxification: A tool for identifying new compounds that revert multidrug resistance
Martín-Cordero, Carmen
Sánchez-Picó, Ángeles
León-González, Antonio J.
Pérez-Pulido, Antonio J.
Daga, Rafael R.
ABC transporter
ABC inhibitor/modulator/chemosensitizer
Cancer chemotherapy
Drug screen
Efflux pump
Multidrug resistance
During tumour progression, cells accumulate secondary mutations and/or chromosomal aberrations that generate genetic diversity within the tumour cell population. This may result in the acquisition of new properties that increase tumour malignancy, such as invasiveness or resistance to chemotherapy. One of the important mechanisms of chemotherapy resistance is overexpression or biochemical activation of ABC family transporters. ABC transporters remove antitumour drugs from the cell, reducing their intracellular concentration and producing resistance against a wide range of chemically unrelated drugs, known as multidrug resistant phenotype (MDR). During recent decades, much effort has been devoted to the isolation of compounds able to inhibit the activity of these transporters. However, few such compounds have reached clinical practice and MDR remains a serious complication in cancer therapy. In an innovative approach to finding new ABC inhibitors, we propose using fission yeast Schizosaccharomyces pombe as a biosensor of detoxification that would enable cost-efficient screening of natural compounds and chemical libraries for molecules that revert the MDR phenotype. Existing fission yeast tools provide genetic, biochemical and cell biological analysis, thereby facilitating identification of drug targets. Putative inhibitors and modulators of ABC transporters could be used in combination with chemotherapeutic drugs for the treatment of multidrug resistant tumours.
Peer reviewed
2016-02-16T13:09:08Z
2016-02-16T13:09:08Z
2013
artículo
http://purl.org/coar/resource_type/c_6501
Current Drug Targets 14(9): 964-985 (2013)
1389-4501
http://hdl.handle.net/10261/129140
10.2174/1389450111314090005
1873-5592
en
http://dx.doi.org/10.2174/1389450111314090005
Sí
none
Bentham Science Publishers