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Published on: January 22, 2019

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

Chunhong Yan1, Md S Jamaluddin, Bharat Aggarwal

  • 1Department of Cancer Biology, University of Texas, M.D. Anderson Cancer Center, Houston, TX 77030, USA.

Molecular Cancer Therapeutics
|February 17, 2005
PubMed

Insights

Curcumin, a compound with known antitumor effects, was studied to find new molecular targets. Gene expression profiling identified activating transcription factor 3 (ATF3) as a key player in curcumin

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Pharmacology

Background:

  • Curcumin (diferuloylmethane) exhibits established antitumor properties.
  • Unbiased studies to identify novel molecular targets of curcumin are lacking.
  • Understanding curcumin's molecular mechanisms is crucial for therapeutic development.

Purpose of the Study:

  • To identify novel molecular targets of curcumin using gene expression profiling.
  • To investigate the role of identified targets in curcumin's antitumor effects.
  • To elucidate the contribution of activating transcription factor 3 (ATF3) to curcumin-induced apoptosis.

Main Methods:

  • Gene expression profiling using a cDNA array with 12,625 probes.
  • Comparison of gene expression in curcumin-treated versus untreated MDA-1986 cells.
  • Quantitative analysis of mRNA and protein levels for key identified genes, including ATF3.

Main Results:

  • Identified 202 up-regulated and 505 down-regulated mRNAs (≥2-fold change).
  • Notable up-regulation of proapoptotic ATF3 (>4-fold), growth regulators (Mad, p27kip1), and phosphatases (CL 100, MKP-5).
  • Significant down-regulation of Frizzled-1 (8-fold), growth-related genes (K-sam, HER3), and E2F-5 transcription factor.

Conclusions:

  • Novel molecular targets of curcumin, including ATF3, have been identified.
  • Activating transcription factor 3 (ATF3) plays a significant role in mediating curcumin's proapoptotic effects.
  • Curcumin's antitumor activity involves modulation of multiple signaling pathways regulating apoptosis and cell growth.

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