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 II 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 etoposide-selective 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.
| Original language | English |
|---|---|
| Pages (from-to) | 2178-2187 |
| Number of pages | 10 |
| Journal | Molecular Cancer Therapeutics |
| Volume | 6 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - 2007 Aug 1 |
Fingerprint
ASJC Scopus subject areas
- Oncology
- Drug Discovery
- Pharmacology
Cite this
Selective cell death of oncogenic Akt-transduced brain cancer cells by etoposide through reactive oxygen species-mediated damage. / Oh, Se Yeong; Sohn, Young Woo; Park, Jong Whi; Park, Hyo Jung; Jeon, Hye Min; Kim, Tae Kyung; Lee, Joong Seob; Jung, Ji Eun; Jin, Xun; Chung, Yong Gu; Choi, Young Ki; You, Seungkwon; Lee, Jang Bo; Kim, Hyunggee.
In: Molecular Cancer Therapeutics, Vol. 6, No. 8, 01.08.2007, p. 2178-2187.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Selective cell death of oncogenic Akt-transduced brain cancer cells by etoposide through reactive oxygen species-mediated damage
AU - Oh, Se Yeong
AU - Sohn, Young Woo
AU - Park, Jong Whi
AU - Park, Hyo Jung
AU - Jeon, Hye Min
AU - Kim, Tae Kyung
AU - Lee, Joong Seob
AU - Jung, Ji Eun
AU - Jin, Xun
AU - Chung, Yong Gu
AU - Choi, Young Ki
AU - You, Seungkwon
AU - Lee, Jang Bo
AU - Kim, Hyunggee
PY - 2007/8/1
Y1 - 2007/8/1
N2 - 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 II 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 etoposide-selective 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.
AB - 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 II 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 etoposide-selective 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.
UR - http://www.scopus.com/inward/record.url?scp=34548101114&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34548101114&partnerID=8YFLogxK
U2 - 10.1158/1535-7163.MCT-07-0111
DO - 10.1158/1535-7163.MCT-07-0111
M3 - Article
C2 - 17699715
AN - SCOPUS:34548101114
VL - 6
SP - 2178
EP - 2187
JO - Molecular Cancer Therapeutics
JF - Molecular Cancer Therapeutics
SN - 1535-7163
IS - 8
ER -