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A cell-permeable dominant-negative survivin protein induces apoptosis and sensitizes prostate cancer cells to TNF-α therapy

Cheung, Chun Hei Antonio, Sun, Xueying, Kanwar, Jagat R., Bai, Ji-Zhong, Cheng, LiTing and Krissansen, Geoffrey W. 2010, A cell-permeable dominant-negative survivin protein induces apoptosis and sensitizes prostate cancer cells to TNF-α therapy, Cancer cell international, vol. 10, no. 1, 36, pp. 1-11.

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Title A cell-permeable dominant-negative survivin protein induces apoptosis and sensitizes prostate cancer cells to TNF-α therapy
Author(s) Cheung, Chun Hei Antonio
Sun, Xueying
Kanwar, Jagat R.
Bai, Ji-Zhong
Cheng, LiTing
Krissansen, Geoffrey W.
Journal name Cancer cell international
Volume number 10
Issue number 1
Season 36
Start page 1
End page 11
Total pages 11
Publisher BioMed Central Ltd.
Place of publication London, England
Publication date 2010-10-28
ISSN 1475-2867
Summary BACKGROUND: Survivin is a member of the inhibitor-of-apoptosis (IAP) family which is widely expressed by many different cancers. Overexpression of survivin is associated with drug resistance in cancer cells, and reduced patient survival after chemotherapy and radiotherapy. Agents that antagonize the function of survivin hold promise for treating many forms of cancer. The purpose of this study was to investigate whether a cell-permeable dominant-negative survivin protein would demonstrate bioactivity against prostate and cervical cancer cells grown in three dimensional culture.

RESULTS: A dominant-negative survivin (C84A) protein fused to the cell penetrating peptide poly-arginine (R9) was expressed in E. coli and purified by affinity chromatography. Western blot analysis revealed that dNSurR9-C84A penetrated into 3D-cultured HeLa and DU145 cancer cells, and a cell viability assay revealed it induced cancer cell death. It increased the activities of caspase-9 and caspase-3, and rendered DU145 cells sensitive to TNF-α via by a mechanism involving activation of caspase-8.

CONCLUSIONS: The results demonstrate that antagonism of survivin function triggers the apoptosis of prostate and cervical cancer cells grown in 3D culture. It renders cancer cells sensitive to the proapoptotic affects of TNF-α, suggesting that survivin blocks the extrinsic pathway of apoptosis. Combination of the biologically active dNSurR9-C84A protein or other survivin antagonists with TNF-α therapy warrants consideration as an approach to cancer therapy.
Notes Published online 2010 October 1. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Language eng
Field of Research 060199 Biochemistry and Cell Biology not elsewhere classified
Socio Economic Objective 970111 Expanding Knowledge in the Medical and Health Sciences
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2010, Cheung et al; licensee BioMed Central Ltd.
Persistent URL http://hdl.handle.net/10536/DRO/DU:30031509

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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.