Assessment of the effect of sphingosine kinase inhibitors on apoptosis,unfolded protein response and autophagy of T-cell acute lymphoblastic leukemia cells; indications for novel therapeutics
Author
Evangelisti, Cecilia; Evangelisti, Camilla; Teti, Gabriella; Chiarini, Francesca; Falconi, Mirella; Melchionda, Fraia; Pession, Andrea; Bertaina, Alice; Locatelli, Franco; McCubrey, James A.; Beak, Dong Jae; Bittman, Robert; Pyne, Susan; Pyne, Nigel J.; Martelli, Alberto M.
Abstract
Sphingosine 1-phosphate (S1P) is a bioactive lipid that is formed by the phosphorylation of sphingosine and catalysed by sphingosine kinase 1 (SK1) or sphingosine kinase 2 (SK2). Sphingosine kinases play a fundamental role in many signaling pathways associated with cancer, suggesting that proteins belonging to this signaling network represent potential therapeutic targets. Over the last years, many improvements have been made in the treatment of T-cell acute lymphoblastic leukemia (T-ALL); however, novel and less toxic therapies are still needed, especially for relapsing and chemo-resistant patients. Here, we analyzed the therapeutic potential of SKi and ROMe, a sphingosine kinase 1 and 2 inhibitor and SK2-selective inhibitor, respectively. While SKi induced apoptosis, ROMe initiated an autophagic cell death in our in vitro cell models. SKi treatment induced an increase in SK1 protein levels in Molt-4 cells, whereas it activated the endoplasmic reticulum (ER) stress/unfolded protein response (UPR) pathway in Jurkat and CEM-R cells as protective mechanisms in a sub-population of T-ALL cells. Interestingly, we observed a synergistic effect of SKi with the classical chemotherapeutic drug vincristine. In addition, we reported that SKi affected signaling cascades implicated in survival, proliferation and stress response of cells. These findings indicate that SK1 or SK2 represent potential targets for treating T-ALL.
Date
2014-09
Citation:
APA:
Evangelisti, Cecilia, & Evangelisti, Camilla, & Teti, Gabriella, & Chiarini, Francesca, & Falconi, Mirella, & Melchionda, Fraia, & Pession, Andrea, & Bertaina, Alice, & Locatelli, Franco, & McCubrey, James A., & Beak, Dong Jae, & Bittman, Robert, & Pyne, Susan, & Pyne, Nigel J., & Martelli, Alberto M.. (September 2014).
Assessment of the effect of sphingosine kinase inhibitors on apoptosis,unfolded protein response and autophagy of T-cell acute lymphoblastic leukemia cells; indications for novel therapeutics.
Oncotarget,
5(17),
7886-
7901. Retrieved from
http://hdl.handle.net/10342/5679
MLA:
Evangelisti, Cecilia, and Evangelisti, Camilla, and Teti, Gabriella, and Chiarini, Francesca, and Falconi, Mirella, and Melchionda, Fraia, and Pession, Andrea, and Bertaina, Alice, and Locatelli, Franco, and McCubrey, James A., and Beak, Dong Jae, and Bittman, Robert, and Pyne, Susan, and Pyne, Nigel J., and Martelli, Alberto M..
"Assessment of the effect of sphingosine kinase inhibitors on apoptosis,unfolded protein response and autophagy of T-cell acute lymphoblastic leukemia cells; indications for novel therapeutics". Oncotarget.
5:17. (7886-7901),
September 2014.
November 30, 2023.
http://hdl.handle.net/10342/5679.
Chicago:
Evangelisti, Cecilia and Evangelisti, Camilla and Teti, Gabriella and Chiarini, Francesca and Falconi, Mirella and Melchionda, Fraia and Pession, Andrea and Bertaina, Alice and Locatelli, Franco and McCubrey, James A. and Beak, Dong Jae and Bittman, Robert and Pyne, Susan and Pyne, Nigel J. and Martelli, Alberto M.,
"Assessment of the effect of sphingosine kinase inhibitors on apoptosis,unfolded protein response and autophagy of T-cell acute lymphoblastic leukemia cells; indications for novel therapeutics," Oncotarget 5, no.
17 (September 2014),
http://hdl.handle.net/10342/5679 (accessed
November 30, 2023).
AMA:
Evangelisti, Cecilia, Evangelisti, Camilla, Teti, Gabriella, Chiarini, Francesca, Falconi, Mirella, Melchionda, Fraia, Pession, Andrea, Bertaina, Alice, Locatelli, Franco, McCubrey, James A., Beak, Dong Jae, Bittman, Robert, Pyne, Susan, Pyne, Nigel J., Martelli, Alberto M..
Assessment of the effect of sphingosine kinase inhibitors on apoptosis,unfolded protein response and autophagy of T-cell acute lymphoblastic leukemia cells; indications for novel therapeutics. Oncotarget.
September 2014;
5(17):
7886-7901.
http://hdl.handle.net/10342/5679. Accessed
November 30, 2023.
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