Resveratrol-induced apoptosis is mediated by early growth response-1, Krüppel-like factor 4, and activating

Nichelle C Whitlock1, Jae Hoon Bahn, Seong-Ho Lee

  • 1Laboratory of Environmental Carcinogenesis, Department of Pathobiology, College of Veterinary Medicine, University of Tennessee, Knoxville, Tennesse 37996, USA.

Insights

Resveratrol boosts activating transcription factor 3 (ATF3) in colorectal cancer cells by regulating Egr-1 and KLF4. This mechanism contributes to resveratrol's antitumorigenic effects and apoptosis induction.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Nutritional Biochemistry

Background:

  • Resveratrol, a natural compound, shows potential antitumorigenic effects in colorectal cancer.
  • The precise molecular mechanisms underlying resveratrol's action remain incompletely elucidated.

Purpose of the Study:

  • To investigate resveratrol's impact on gene expression in human colorectal cancer cells.
  • To identify key genes and pathways involved in resveratrol's antitumorigenic activity.

Main Methods:

  • Gene expression analysis (mRNA and protein levels) following resveratrol treatment.
  • Promoter analysis, electrophoretic mobility shift assays (EMSA), and chromatin immunoprecipitation (ChIP) to study transcriptional regulation.
  • Assessment of apoptosis induction.

Main Results:

  • Resveratrol significantly upregulates activating transcription factor 3 (ATF3) expression.
  • Resveratrol-mediated ATF3 induction involves the transcription factors Early Growth Response-1 (Egr-1) and Krüppel-like Factor 4 (KLF4).
  • Egr-1 and KLF4 interact in the presence of resveratrol, facilitating ATF3 transcriptional regulation and contributing to resveratrol-induced apoptosis.

Conclusions:

  • Resveratrol enhances ATF3 expression through Egr-1 and KLF4 interaction, providing a novel mechanism for its transcriptional regulation.
  • Increased ATF3 expression is a key mediator of resveratrol's ability to induce apoptosis in colorectal cancer cells.
  • These findings offer a deeper understanding of resveratrol's chemopreventive and therapeutic potential against colorectal cancer.

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