Doxorubicin prevents endoplasmic reticulum stress-induced apoptosis

Soo Jung Kim, Kyung Mi Park, Nayoung Kim, Young Il Yeom

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)463-468
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume339
Issue number2
DOIs
StatePublished - Jan 13 2006
Externally publishedYes

Fingerprint

Endoplasmic Reticulum Stress
Doxorubicin
Apoptosis
Unfolded Protein Response
Thapsigargin
Topoisomerase Inhibitors
Cell death
Activating Transcription Factor 4
Cell Death
Transcription Factor CHOP
Proteins
Eukaryotic Cells
Etoposide
Transcription
Protein C
Cell Communication
Down-Regulation
Cells
Breast Neoplasms
Messenger RNA

Keywords

  • Apoptosis
  • Doxorubicin
  • Stress signaling
  • Thapsigargin
  • Unfolded protein response

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Doxorubicin prevents endoplasmic reticulum stress-induced apoptosis. / Kim, Soo Jung; Park, Kyung Mi; Kim, Nayoung; Yeom, Young Il.

In: Biochemical and Biophysical Research Communications, Vol. 339, No. 2, 13.01.2006, p. 463-468.

Research output: Contribution to journalArticle

Kim, Soo Jung ; Park, Kyung Mi ; Kim, Nayoung ; Yeom, Young Il. / Doxorubicin prevents endoplasmic reticulum stress-induced apoptosis. In: Biochemical and Biophysical Research Communications. 2006 ; Vol. 339, No. 2. pp. 463-468.
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