Journal article
Selective cell death of oncogenic Akt-transduced brain cancer cells by etoposide through reactive oxygen species-mediated damage
Molecular cancer therapeutics, Vol.6(8), pp.2178-2187
08/01/2007
DOI: 10.1158/1535-7163.MCT-07-0111
PMID: 17699715
Abstract
We have established several glioma-relevant oncogene-engineered cancer cells to reevaluate the oncogene-selective cytotoxicity of previously well-characterized anticancer drugs, such as etoposide, doxorubicin, staurosporine, and carmustine. Among several glioma-relevant oncogenes (activated epidermal growth factor receptor, Ras, and Akt, as well as Bcl-2 and p53DD used in the present study), the activated epidermal growth factor receptor, Ras, and Akt exerted oncogenic transformation of Ink4a/Arf(-/-) murine astrocyte cells. We identified that etoposide, a topoisomerase 11 inhibitor, caused selective killing of myristylated Akt (Akt-myr) - transduced Ink4a/Arf(-/-) astrocytes and U87MG cells in a dose- and time-dependent manner. Etoposide-selective cytotoxicity in the Akt-myr - transduced cells was shown to be caused by nonapoptotic cell death and occurred in a p53-independent manner. Etoposide caused severe reactive oxygen species (ROS) accumulation preferentially in the Akt-myr-transduced cells, and elevated ROS rendered these cells highly sensitive to cell death. The etoposideselective cell death of Akt-myr-transduced cells was attenuated by pepstatin A, a lysosomal protease inhibitor. In the present study, we show that etoposide might possess a novel therapeutic activity for oncogenic Akt-transduced cancer cells to kill preferentially through ROS-mediated-damage.
Details
- Title: Subtitle
- Selective cell death of oncogenic Akt-transduced brain cancer cells by etoposide through reactive oxygen species-mediated damage
- Creators
- Se-Yeong OhYoung-Woo SohnJong-Whi ParkHyo-Jung ParkHye-Min JeonTae-Kyung KimJoong-Seob LeeJi-Eun JungXun JinYong Gu Chung - Korea UniversityYoung-Ki Choi - Chungbuk National UniversitySeungkwon YouJang-Bo Lee - Korea UniversityHyunggee Kim
- Resource Type
- Journal article
- Publication Details
- Molecular cancer therapeutics, Vol.6(8), pp.2178-2187
- Publisher
- Amer Assoc Cancer Research
- DOI
- 10.1158/1535-7163.MCT-07-0111
- PMID
- 17699715
- ISSN
- 1535-7163
- eISSN
- 1538-8514
- Number of pages
- 10
- Language
- English
- Date published
- 08/01/2007
- Academic Unit
- Neurosurgery
- Record Identifier
- 9984459623302771
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