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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
The multikinase inhibitor Sorafenib displays significant antiproliferative effects and induces apoptosis via caspase 3, 7 and PARP in B- and T-lymphoblastic cells
BMC Cancer, Volume 10, Article 560, Year 2010
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Description
Background: Targeted therapy approaches have been successfully introduced into the treatment of several cancers. The multikinase inhibitor Sorafenib has antitumor activity in solid tumors and its effects on acute lymphoblastic leukemia (ALL) cells are still unclear.Methods: ALL cell lines (SEM, RS4;11 and Jurkat) were treated with Sorafenib alone or in combination with cytarabine, doxorubicin or RAD001. Cell count, apoptosis and necrosis rates, cell cycle distribution, protein phosphorylation and metabolic activity were determined.Results: Sorafenib inhibited the proliferation of ALL cells by cell cycle arrest accompanied by down-regulation of CyclinD3 and CDK4. Furthermore, Sorafenib initiated apoptosis by cleavage of caspases 3, 7 and PARP. Apoptosis and necrosis rates increased significantly with most pronounced effects after 96 h. Antiproliferative effects of Sorafenib were associated with a decreased phosphorylation of Akt (Ser473 and Thr308), FoxO3A (Thr32) and 4EBP-1 (Ser65 and Thr70) as early as 0.5 h after treatment. Synergistic effects were seen when Sorafenib was combined with other cytotoxic drugs or a mTOR inhibitor emphasizing the Sorafenib effect.Conclusion: Sorafenib displays significant antileukemic activity in vitro by inducing cell cycle arrest and apoptosis. Furthermore, it influences PI3K/Akt/mTOR signaling in ALL cells. © 2010 Schult et al; licensee BioMed Central Ltd.
Authors & Co-Authors
Glass, Aenne
Germany, Rostock
Universität Rostock
Fuellen, Georg F.
Germany, Rostock
Universität Rostock
Wolkenhauer, Olaf
Germany, Rostock
Universität Rostock
Neri, L. M.
Italy, Ferrara
University of Ferrara
Junghanss, Christian
Germany, Rostock
Universität Rostock
Statistics
Citations: 38
Authors: 5
Affiliations: 2
Identifiers
Doi:
10.1186/1471-2407-10-560
ISSN:
14712407
Research Areas
Cancer
Noncommunicable Diseases