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Increased expression of cdc2 inhibits transport function of RLIP76 and promotes apoptosis.
- Source :
-
Cancer letters [Cancer Lett] 2009 Oct 08; Vol. 283 (2), pp. 152-8. Date of Electronic Publication: 2009 Apr 17. - Publication Year :
- 2009
-
Abstract
- RLIP76 is a stress-responsive glutathione-electrophile-conjugates (GS-E) and drugs transporter which is over-expressed in different types of cancers. Cdc2 is a cell-cycle check point control kinase which has been shown to bind to RLIP76 during mitosis, such that endocytosis is inhibited. In present studies, we have purified cdc2 and examined its effect on the transport activity of RLIP76 reconstituted into artificial liposomes. Both doxorubicin (DOX) and dinitro-phenyl S-glutathione (DNP-SG) transport were inhibited by cdc2 in a concentration dependent manner. Liposomal delivery of cdc2 to H358 cells caused apoptosis, resulted in an increased intracellular doxorubicin-accumulation and decreased rate of efflux from the cells. In the present communication, we propose that the accumulation-deficient drug-resistance mediated by RLIP76 can be modulated by inhibition of RLIP76 transport activity by cdc2.
- Subjects :
- Antibiotics, Antineoplastic metabolism
CDC2 Protein Kinase
Cell Line, Tumor
Cyclin-Dependent Kinases
Doxorubicin metabolism
Drug Resistance, Neoplasm
Glutathione metabolism
Humans
In Situ Nick-End Labeling
Liposomes
Protein Transport physiology
ATP-Binding Cassette Transporters metabolism
Apoptosis physiology
Cyclin B biosynthesis
GTPase-Activating Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1872-7980
- Volume :
- 283
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Cancer letters
- Publication Type :
- Academic Journal
- Accession number :
- 19375851
- Full Text :
- https://doi.org/10.1016/j.canlet.2009.03.033