Targeting survivin via PI3K but not c-akt/PKB by anticancer drugs in immature neutrophils

Martinelli, S., Kostylina, G., Niggli, V., Baumann, C., Fey, M. F., Wendel, H. G., Lowe, S. W., Yousefi, S., Simon, H. U. (2006) Targeting survivin via PI3K but not c-akt/PKB by anticancer drugs in immature neutrophils. Oncogene, 25 (52). pp. 6915-6923. ISSN 09509232

DOI: 10.1038/sj.onc.1209692


Myelosuppression is the most common unwanted side effect associated with the administration of anticancer drugs, and infections remain a common cause of death in chemotherapy-treated patients. Several mechanisms of the cytotoxicity of these drugs have been proposed and may synergistically operate in a given cell. Survivin expression has been associated with cancer, but recent reports suggest that this molecule is also expressed in several immature and mature hematopoietic cells. Here, we provide evidence that treatment of immature neutrophils with anticancer drugs reduced endogenous survivin levels causing apoptosis. The anticancer drugs did not directly target survivin, instead they blocked the activity of phosphatidylinositol-3-OH kinase, which regulated survivin expression and apoptosis in these cells. Strikingly, and in contrast to other cells, this pathway did not involve the serine/threonine kinase c-akt/PKB. Moreover, in combination with anticancer drug therapy, rapamycin did not induce increased myelosuppression in an experimental lymphoma mouse model. These data suggest that drugs that block either c-akt/PKB or signaling molecules located distal to c-akt/PKB may preferentially induce apoptosis of cancer cells as they exhibit no cytotoxicity for immature neutrophils. © 2006 Nature Publishing Group. All rights reserved.

Item Type: Paper
Subjects: diseases & disorders > cancer
diseases & disorders > cancer > drugs and therapies
organs, tissues, organelles, cell types and functions > organs types and functions > myelosuppression
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > survivin
CSHL Authors:
Communities: CSHL labs > Lowe lab
Depositing User: CSHL Librarian
Date: 2006
Date Deposited: 12 Dec 2011 17:40
Last Modified: 01 Mar 2013 16:38
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