p53 mediates DNA damaging drug-induced apoptosis through a caspase-9-dependent pathway in SH-SY5Y neuroblastoma cells

Hongjuan Cui, Allen Schroering, Hanfei Ding

Research output: Contribution to journalArticle

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Abstract

The signaling pathway for DNA damaging drug-triggered apoptosis was examined in a chemosensitive human neuroblastoma cell line, SH-SY5Y. Doxorubicin and etoposide induce rapid and extensive apoptosis in SH-SY5Y cells. After the drug treatment, p53 protein levels increase in the nucleus, leading to the induction of its transcription targets p21Waf1/Cip1 and MDM2. Inactivation of p53, either by the human papillomavirus type 16 E6 protein or by a dominant-negative mutant p53 (R175H), completely protects SH-SY5Y cells from drug-triggered apoptosis. Cytochrome c and caspase-9 function downstream of p53 in mediating the drug-triggered apoptosis in SH-SY5Y cells. In drug-treated cells, cytochrome c is released, and caspase-9 becomes activated. Inactivation of p53 blocks cytochrome c release and caspase-9 activation. Furthermore, drug-induced cell death can be prevented by expression of a dominant-negative mutant of caspase-9. These findings define a molecular pathway for mediating DNA damaging drug-induced apoptosis in the human neuroblastoma SH-SY5Y cells and suggest that inactivation of essential components of this apoptotic pathway may confer drug resistance on neuroblastoma cells.

Original languageEnglish (US)
Pages (from-to)679-686
Number of pages8
JournalMolecular Cancer Therapeutics
Volume1
Issue number9
StatePublished - Jul 1 2002
Externally publishedYes

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Caspase 9
Neuroblastoma
Apoptosis
DNA
Pharmaceutical Preparations
Cytochromes c
Etoposide
Drug Resistance
Doxorubicin
Cell Death
Cell Line

ASJC Scopus subject areas

  • Oncology
  • Cancer Research
  • Drug Discovery
  • Pharmacology

Cite this

p53 mediates DNA damaging drug-induced apoptosis through a caspase-9-dependent pathway in SH-SY5Y neuroblastoma cells. / Cui, Hongjuan; Schroering, Allen; Ding, Hanfei.

In: Molecular Cancer Therapeutics, Vol. 1, No. 9, 01.07.2002, p. 679-686.

Research output: Contribution to journalArticle

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