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

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Abstract

Since epithelial-mesenchymal transition (EMT) plays a critical role in cancer progression and in maintaining cancer stem cell properties, EMT is emerging as a therapeutic target for inhibiting the metastatic progression of cancer cells. 2′-Hydroxycinnamaldehyde (HCA) and its derivative, 2′-benzoyloxycinnamaldehyde, have recently been suggested as promising therapeutic candidates for cancer treatment. The purpose of this study is to investigate the anti-metastatic effect of HCA on breast cancer and the molecular mechanisms by which HCA regulates the transcriptional program during EMT. HCA induces epithelial reversion at nanomolar concentrations by suppressing Snail via the nuclear translocalization of GSK-3β, which results in the transcriptional upregulation of E-cadherin. HCA also activates the transcription factor KLF17, which suppresses Id-1, indicating that HCA inhibits EMT by multiple transcriptional programs. Further, HCA treatment significantly inhibits lung metastasis in a mouse orthotopic breast cancer model. This study demonstrates the anti-metastatic effect of the non-toxic natural compound HCA through attenuation of EMT in a breast cancer model.

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Acknowledgments

This work was supported by the Basic Science Research Program through the National Research Foundation of Korea Grant funded by the Korean Government (2009-0070462). This research was supported by the Bio & Medical Technology Development Program of the National Research Foundation funded by the Korean government (2012M3A9C404877).

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Authors and Affiliations

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

    Ismail Ahmed Ismail, Hye Sook Kang, Heon-Jin Lee & Su-Hyung Hong

  2. Laboratory of Chemical Biology and Genomics, Korea Research Institute of Bioscience and Biotechnology, University of Science and Technology, Daejon, 305-806, Republic of Korea

    Hyeyoun Chang & Byoung-Mog Kwon

  3. Bio-Evaluation Center, Korea Research Institute of Bioscience and Biotechnology, Chungbuk, Republic of Korea

    Jieun Yun & Chang Woo Lee

  4. Department of Oral Pathology, Oral Cancer Research Institute, College of Dentistry, Yonsei University, Seoul, 120-752, Republic of Korea

    Nam Hee Kim, Hyun Sil Kim & Jong In Yook

  5. Laboratory of Molecular Cell Biology, Department of Zoology, Faculty of Science, Assiut University, Assiut, 71516, Egypt

    Ismail Ahmed Ismail

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  1. Ismail Ahmed Ismail
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  2. Hye Sook Kang
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Correspondence to Su-Hyung Hong or Byoung-Mog Kwon.

Additional information

I. A. Ismail and H. S. Kang contributed equally to this work.

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10549_2012_2388_MOESM1_ESM.pdf

Relative cell invasion (a) and basal mRNA expression level changes in KLF17 (b), Sp1 (c), and Id-1 (d) after HCA treatment in non-metastatic (MCF-7, T47D) and metastatic (MDA-MB-231, MDA-MB-435) cells. These results are from three independent experiments and each bar represents standard deviation. (PDF 47 kb)

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Ismail, I.A., Kang, H.S., Lee, HJ. et al. 2-Hydroxycinnamaldehyde inhibits the epithelial-mesenchymal transition in breast cancer cells. Breast Cancer Res Treat 137, 697–708 (2013). https://doi.org/10.1007/s10549-012-2388-7

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