2-Hydroxycinnamaldehyde inhibits the epithelial-mesenchymal transition in breast cancer cells

Ismail Ahmed Ismail1, Hye Sook Kang, Heon-Jin Lee

  • 1Department of Oral Microbiology, School of Dentistry, Kyungpook National University, Daegu, Republic of Korea.

Insights

The natural compound 2'-Hydroxycinnamaldehyde (HCA) effectively inhibits breast cancer metastasis by reversing epithelial-mesenchymal transition (EMT). HCA targets key molecular pathways, offering a promising non-toxic therapeutic strategy for advanced cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Epithelial-mesenchymal transition (EMT) is crucial for cancer progression and metastasis.
  • EMT is a key target for anti-cancer therapies aiming to inhibit cancer spread.
  • 2'-Hydroxycinnamaldehyde (HCA) shows potential as a therapeutic agent for cancer treatment.

Purpose of the Study:

  • To investigate the anti-metastatic effects of HCA on breast cancer.
  • To elucidate the molecular mechanisms by which HCA regulates EMT.
  • To evaluate HCA's impact on the transcriptional program during EMT.

Main Methods:

  • Investigated HCA's effect on EMT markers in breast cancer cells.
  • Analyzed the role of GSK-3β and Snail in HCA-mediated epithelial reversion.
  • Assessed the activation of KLF17 and suppression of Id-1 by HCA.
  • Evaluated HCA's efficacy in inhibiting lung metastasis in a mouse orthotopic breast cancer model.

Main Results:

  • HCA induced epithelial reversion at nanomolar concentrations by suppressing Snail via GSK-3β nuclear translocation.
  • HCA treatment led to the transcriptional upregulation of E-cadherin.
  • HCA activated KLF17, which suppressed Id-1, indicating multi-pathway inhibition of EMT.
  • HCA significantly inhibited lung metastasis in vivo.

Conclusions:

  • HCA demonstrates significant anti-metastatic effects in breast cancer by attenuating EMT.
  • HCA acts through multiple transcriptional programs to inhibit EMT, including Snail suppression and KLF17 activation.
  • HCA is a non-toxic natural compound with therapeutic potential for inhibiting cancer metastasis.

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