Gene expression profiling identifies activating transcription factor 3 as a novel contributor to the proapoptotic effect of curcumin

Chunhong Yan, Md S. Jamaluddin, Bharat Aggarwal, Jeffrey Myers, Douglas D. Boyd

Research output: Contribution to journalArticle

102 Citations (Scopus)

Abstract

The antitumor effect of curcumin (diferuloylmethane) is well established. However, there have been no unbiased studies to identify novel molecular targets of this compound. We therefore undertook a gene expression profiling study to identify novel targets of curcumin. A cDNA array comprised of 12,625 probes was used to compare total RNA extracted from curcumin-treated and -untreated MDA-1986 cells for differential gene expression. We identified 202 up-regulated mRNAs and 505 transcripts decreased ≥2-fold. The proapoptotic activating transcription factor 3 (ATF3) was induced >4-fold. Two negative regulators of growth control [antagonizer of myc transcriptional activity (Mad) and p27kip1] were induced 68- and 3-fold, respectively. Additionally, two dual-activity phosphatases (CL 100 and MKP-5), which inactivate the c-jun-NH2-kinases, showed augmented expression, coinciding with reduced expression of the upstream activators of c-jun-NH2-kinase (MEKK and MKK4). Of the repressed genes, the expression of Frizzled-1 (Wnt receptor) was most strongly attenuated (8-fold). Additionally, two genes implicated in growth control (K-sam, encoding the keratinocyte growth factor receptor, and HER3) as well as the E2F-5 transcription factor, which regulates genes controlling cell proliferation, also showed down-regulated expression. Considering its role in apoptosis, we determined the contribution of ATF3 to the antitumor effect of curcumin. Curcumin-treated MDA-1986 cells showed a rapid, dose-dependent increase in ATF3/mRNA protein. Moreover, expression of an exogenous ATF3 cDNA synergized with curcumin in inducing apoptosis. Thus, we have identified several putative, novel molecular targets of curcumin and showed that one, ATF3, contributes to the proapoptotic effects of this compound.

Original languageEnglish (US)
Pages (from-to)233-241
Number of pages9
JournalMolecular Cancer Therapeutics
Volume4
Issue number2
StatePublished - Feb 1 2005
Externally publishedYes

Fingerprint

Activating Transcription Factor 3
Curcumin
Gene Expression Profiling
E2F5 Transcription Factor
Phosphotransferases
Wnt Receptors
Apoptosis
MAP Kinase Kinase Kinases
Gene Expression
Messenger RNA
Growth
Oligonucleotide Array Sequence Analysis
Phosphoric Monoester Hydrolases
Genes
Complementary DNA
Cell Proliferation
RNA

ASJC Scopus subject areas

  • Oncology
  • Drug Discovery
  • Pharmacology

Cite this

Gene expression profiling identifies activating transcription factor 3 as a novel contributor to the proapoptotic effect of curcumin. / Yan, Chunhong; Jamaluddin, Md S.; Aggarwal, Bharat; Myers, Jeffrey; Boyd, Douglas D.

In: Molecular Cancer Therapeutics, Vol. 4, No. 2, 01.02.2005, p. 233-241.

Research output: Contribution to journalArticle

Yan, Chunhong ; Jamaluddin, Md S. ; Aggarwal, Bharat ; Myers, Jeffrey ; Boyd, Douglas D. / Gene expression profiling identifies activating transcription factor 3 as a novel contributor to the proapoptotic effect of curcumin. In: Molecular Cancer Therapeutics. 2005 ; Vol. 4, No. 2. pp. 233-241.
@article{913b5876b5c945c191c03e9a83bf9e88,
title = "Gene expression profiling identifies activating transcription factor 3 as a novel contributor to the proapoptotic effect of curcumin",
abstract = "The antitumor effect of curcumin (diferuloylmethane) is well established. However, there have been no unbiased studies to identify novel molecular targets of this compound. We therefore undertook a gene expression profiling study to identify novel targets of curcumin. A cDNA array comprised of 12,625 probes was used to compare total RNA extracted from curcumin-treated and -untreated MDA-1986 cells for differential gene expression. We identified 202 up-regulated mRNAs and 505 transcripts decreased ≥2-fold. The proapoptotic activating transcription factor 3 (ATF3) was induced >4-fold. Two negative regulators of growth control [antagonizer of myc transcriptional activity (Mad) and p27kip1] were induced 68- and 3-fold, respectively. Additionally, two dual-activity phosphatases (CL 100 and MKP-5), which inactivate the c-jun-NH2-kinases, showed augmented expression, coinciding with reduced expression of the upstream activators of c-jun-NH2-kinase (MEKK and MKK4). Of the repressed genes, the expression of Frizzled-1 (Wnt receptor) was most strongly attenuated (8-fold). Additionally, two genes implicated in growth control (K-sam, encoding the keratinocyte growth factor receptor, and HER3) as well as the E2F-5 transcription factor, which regulates genes controlling cell proliferation, also showed down-regulated expression. Considering its role in apoptosis, we determined the contribution of ATF3 to the antitumor effect of curcumin. Curcumin-treated MDA-1986 cells showed a rapid, dose-dependent increase in ATF3/mRNA protein. Moreover, expression of an exogenous ATF3 cDNA synergized with curcumin in inducing apoptosis. Thus, we have identified several putative, novel molecular targets of curcumin and showed that one, ATF3, contributes to the proapoptotic effects of this compound.",
author = "Chunhong Yan and Jamaluddin, {Md S.} and Bharat Aggarwal and Jeffrey Myers and Boyd, {Douglas D.}",
year = "2005",
month = "2",
day = "1",
language = "English (US)",
volume = "4",
pages = "233--241",
journal = "Molecular Cancer Therapeutics",
issn = "1535-7163",
publisher = "American Association for Cancer Research Inc.",
number = "2",

}

TY - JOUR

T1 - Gene expression profiling identifies activating transcription factor 3 as a novel contributor to the proapoptotic effect of curcumin

AU - Yan, Chunhong

AU - Jamaluddin, Md S.

AU - Aggarwal, Bharat

AU - Myers, Jeffrey

AU - Boyd, Douglas D.

PY - 2005/2/1

Y1 - 2005/2/1

N2 - The antitumor effect of curcumin (diferuloylmethane) is well established. However, there have been no unbiased studies to identify novel molecular targets of this compound. We therefore undertook a gene expression profiling study to identify novel targets of curcumin. A cDNA array comprised of 12,625 probes was used to compare total RNA extracted from curcumin-treated and -untreated MDA-1986 cells for differential gene expression. We identified 202 up-regulated mRNAs and 505 transcripts decreased ≥2-fold. The proapoptotic activating transcription factor 3 (ATF3) was induced >4-fold. Two negative regulators of growth control [antagonizer of myc transcriptional activity (Mad) and p27kip1] were induced 68- and 3-fold, respectively. Additionally, two dual-activity phosphatases (CL 100 and MKP-5), which inactivate the c-jun-NH2-kinases, showed augmented expression, coinciding with reduced expression of the upstream activators of c-jun-NH2-kinase (MEKK and MKK4). Of the repressed genes, the expression of Frizzled-1 (Wnt receptor) was most strongly attenuated (8-fold). Additionally, two genes implicated in growth control (K-sam, encoding the keratinocyte growth factor receptor, and HER3) as well as the E2F-5 transcription factor, which regulates genes controlling cell proliferation, also showed down-regulated expression. Considering its role in apoptosis, we determined the contribution of ATF3 to the antitumor effect of curcumin. Curcumin-treated MDA-1986 cells showed a rapid, dose-dependent increase in ATF3/mRNA protein. Moreover, expression of an exogenous ATF3 cDNA synergized with curcumin in inducing apoptosis. Thus, we have identified several putative, novel molecular targets of curcumin and showed that one, ATF3, contributes to the proapoptotic effects of this compound.

AB - The antitumor effect of curcumin (diferuloylmethane) is well established. However, there have been no unbiased studies to identify novel molecular targets of this compound. We therefore undertook a gene expression profiling study to identify novel targets of curcumin. A cDNA array comprised of 12,625 probes was used to compare total RNA extracted from curcumin-treated and -untreated MDA-1986 cells for differential gene expression. We identified 202 up-regulated mRNAs and 505 transcripts decreased ≥2-fold. The proapoptotic activating transcription factor 3 (ATF3) was induced >4-fold. Two negative regulators of growth control [antagonizer of myc transcriptional activity (Mad) and p27kip1] were induced 68- and 3-fold, respectively. Additionally, two dual-activity phosphatases (CL 100 and MKP-5), which inactivate the c-jun-NH2-kinases, showed augmented expression, coinciding with reduced expression of the upstream activators of c-jun-NH2-kinase (MEKK and MKK4). Of the repressed genes, the expression of Frizzled-1 (Wnt receptor) was most strongly attenuated (8-fold). Additionally, two genes implicated in growth control (K-sam, encoding the keratinocyte growth factor receptor, and HER3) as well as the E2F-5 transcription factor, which regulates genes controlling cell proliferation, also showed down-regulated expression. Considering its role in apoptosis, we determined the contribution of ATF3 to the antitumor effect of curcumin. Curcumin-treated MDA-1986 cells showed a rapid, dose-dependent increase in ATF3/mRNA protein. Moreover, expression of an exogenous ATF3 cDNA synergized with curcumin in inducing apoptosis. Thus, we have identified several putative, novel molecular targets of curcumin and showed that one, ATF3, contributes to the proapoptotic effects of this compound.

UR - http://www.scopus.com/inward/record.url?scp=14844319300&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=14844319300&partnerID=8YFLogxK

M3 - Article

C2 - 15713895

AN - SCOPUS:14844319300

VL - 4

SP - 233

EP - 241

JO - Molecular Cancer Therapeutics

JF - Molecular Cancer Therapeutics

SN - 1535-7163

IS - 2

ER -