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Ubiquitin ligase Cbl-b sensitizes leukemia and gastric cancer cells to anthracyclines by activating the mitochondrial pathway and modulating Akt and ERK survival signals
- Source :
- FEBS Letters; Jul2009, Vol. 583 Issue 13, p2255-2262, 8p
- Publication Year :
- 2009
-
Abstract
- Abstract: The present study reported that the ubiquitin ligase Cbl-b was up-regulated during anthracycline-induced apoptosis in two cell lines, RBL-2H3 leukemia cells and MGC803 gastric cancer cells. Overexpression of Cbl-b strongly promoted the cytotoxic and apoptosis-inducing effects of anthracyclines, while a dominant negative (DN) Cbl-b mutation abolished these effects in both cell lines. Further investigation revealed that mitochondrial depolarization was enhanced by Cbl-b and decreased by Cbl-b (DN) in RBL-2H3 cells. Moreover, overexpression of Cbl-b significantly suppressed ERK activation, and Cbl-b (DN) strongly enhanced both ERK and Akt activation. Altogether, these results indicate that Cbl-b sensitized both leukemia and gastric cancer cells to anthracyclines by activating the mitochondrial apoptotic pathway and modulating the ERK and Akt survival pathways. [Copyright &y& Elsevier]
Details
- Language :
- English
- ISSN :
- 00145793
- Volume :
- 583
- Issue :
- 13
- Database :
- Complementary Index
- Journal :
- FEBS Letters
- Publication Type :
- Academic Journal
- Accession number :
- 43035644
- Full Text :
- https://doi.org/10.1016/j.febslet.2009.05.054