TY - JOUR
T1 - Doxorubicin prevents endoplasmic reticulum stress-induced apoptosis
AU - Kim, Soo Jung
AU - Park, Kyung Mi
AU - Kim, Nayoung
AU - Yeom, Young Il
N1 - Funding Information:
This work was supported by the Functional Analysis of the Human Genome Project of the 21C Frontier of the Korean Ministry of Science and Technology.
PY - 2006/1/13
Y1 - 2006/1/13
N2 - Several cellular stress signaling pathways initiate apoptosis in eukaryotic cells, but the interactions and coordination between the pathways have not been elucidated. In this study, apoptosis was triggered in MCF7 human breast carcinoma cells using doxorubicin, a topoisomerase inhibitor, and an endoplasmic reticulum (ER) stress inducer, thapsigargin, the latter causing the unfolded protein response (UPR). Interestingly, compared to treatment with doxorubicin or thapsigargin alone, cell death was reduced by treatment with both stress inducers. In contrast to another topoisomerase inhibitor, etoposide, doxorubicin markedly decreased apoptosis induced by thapsigargin; this doxorubicin effect was accompanied by reduced expression of the UPR-specific proapoptotic protein, C/EBP-homologous protein, and its upstream transcription factor, ATF4. We further found that doxorubicin downregulates the expression of ATF4 mRNA, indicating that doxorubicin interferes with the UPR at the level of ATF4 transcription. Taken together, the data suggest that ER stress-initiated cell death might be regulated by doxorubicin.
AB - Several cellular stress signaling pathways initiate apoptosis in eukaryotic cells, but the interactions and coordination between the pathways have not been elucidated. In this study, apoptosis was triggered in MCF7 human breast carcinoma cells using doxorubicin, a topoisomerase inhibitor, and an endoplasmic reticulum (ER) stress inducer, thapsigargin, the latter causing the unfolded protein response (UPR). Interestingly, compared to treatment with doxorubicin or thapsigargin alone, cell death was reduced by treatment with both stress inducers. In contrast to another topoisomerase inhibitor, etoposide, doxorubicin markedly decreased apoptosis induced by thapsigargin; this doxorubicin effect was accompanied by reduced expression of the UPR-specific proapoptotic protein, C/EBP-homologous protein, and its upstream transcription factor, ATF4. We further found that doxorubicin downregulates the expression of ATF4 mRNA, indicating that doxorubicin interferes with the UPR at the level of ATF4 transcription. Taken together, the data suggest that ER stress-initiated cell death might be regulated by doxorubicin.
KW - Apoptosis
KW - Doxorubicin
KW - Stress signaling
KW - Thapsigargin
KW - Unfolded protein response
UR - http://www.scopus.com/inward/record.url?scp=28444467028&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=28444467028&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2005.11.040
DO - 10.1016/j.bbrc.2005.11.040
M3 - Article
C2 - 16298333
AN - SCOPUS:28444467028
SN - 0006-291X
VL - 339
SP - 463
EP - 468
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 2
ER -