Par-4, a proapoptotic gene, is regulated by NSAIDs in human colon carcinoma cells

Zhonghua Zhang, Raymond N. DuBois

Research output: Contribution to journalArticle

86 Citations (Scopus)

Abstract

Background and Aims: Many reports indicate that nonsteroidal anti- inflammatory drugs (NSAIDs) have antineoplastic effects, but the precise molecular mechanism(s) responsible are unclear. We evaluated the effect of cyclooxygenase (COX) inhibitors (NSAIDs) on human colon carcinoma cells (HCA- 7) and identified several genes that are regulated after treatment with NS- 398, a selective COX-2 inhibitor. Methods: Differential display polymerase chain reaction cloning techniques were used to identify genes regulated by treatment with NSAIDs and selective COX-2 inhibitors. Results: A prostate apoptosis response 4 (Par-4) gene was up-regulated after NSAID treatment. Par-4 was first isolated from prostate carcinoma cells undergoing apoptosis, and expression of Par-4 sensitized cancer cells to apoptotic stimuli. Par-4 levels were increased in cells treated with COX inhibitors such as NS-398, nimesulide, SC-58125, and sulindac sulfide. Treatment of HCA-7 cells with these agents also induced apoptotic cell death. Conclusions: The results suggest that regulation of Par-4 contributes to the proapoptotic effects of high-dose COX inhibitors (NSAIDs) by serving as a downstream mediator leading to initiation of programmed cell death.

Original languageEnglish (US)
Pages (from-to)1012-1017
Number of pages6
JournalGastroenterology
Volume118
Issue number6
StatePublished - 2000
Externally publishedYes

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Prostate
Colon
Anti-Inflammatory Agents
Apoptosis
Carcinoma
Cyclooxygenase Inhibitors
Pharmaceutical Preparations
Genes
Cyclooxygenase 2 Inhibitors
nimesulide
Cell Death
Therapeutics
Antineoplastic Agents
Organism Cloning
Polymerase Chain Reaction
Neoplasms
N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Par-4, a proapoptotic gene, is regulated by NSAIDs in human colon carcinoma cells. / Zhang, Zhonghua; DuBois, Raymond N.

In: Gastroenterology, Vol. 118, No. 6, 2000, p. 1012-1017.

Research output: Contribution to journalArticle

Zhang, Z & DuBois, RN 2000, 'Par-4, a proapoptotic gene, is regulated by NSAIDs in human colon carcinoma cells', Gastroenterology, vol. 118, no. 6, pp. 1012-1017.
Zhang, Zhonghua ; DuBois, Raymond N. / Par-4, a proapoptotic gene, is regulated by NSAIDs in human colon carcinoma cells. In: Gastroenterology. 2000 ; Vol. 118, No. 6. pp. 1012-1017.
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abstract = "Background and Aims: Many reports indicate that nonsteroidal anti- inflammatory drugs (NSAIDs) have antineoplastic effects, but the precise molecular mechanism(s) responsible are unclear. We evaluated the effect of cyclooxygenase (COX) inhibitors (NSAIDs) on human colon carcinoma cells (HCA- 7) and identified several genes that are regulated after treatment with NS- 398, a selective COX-2 inhibitor. Methods: Differential display polymerase chain reaction cloning techniques were used to identify genes regulated by treatment with NSAIDs and selective COX-2 inhibitors. Results: A prostate apoptosis response 4 (Par-4) gene was up-regulated after NSAID treatment. Par-4 was first isolated from prostate carcinoma cells undergoing apoptosis, and expression of Par-4 sensitized cancer cells to apoptotic stimuli. Par-4 levels were increased in cells treated with COX inhibitors such as NS-398, nimesulide, SC-58125, and sulindac sulfide. Treatment of HCA-7 cells with these agents also induced apoptotic cell death. Conclusions: The results suggest that regulation of Par-4 contributes to the proapoptotic effects of high-dose COX inhibitors (NSAIDs) by serving as a downstream mediator leading to initiation of programmed cell death.",
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