2′-Hydroxyflavanone induces apoptosis through Egr-1 involving expression of Bax, p21, and NAG-1 in colon cancer cells

Authors

  • Soon Young Shin,

    1. SMART Institute of Advanced Biomedical Science, Konkuk University, Seoul, Korea
    2. Department of Biomedical Science and Technology, Research Center for Transcription Control, Konkuk University, Seoul, Korea
    Search for more papers by this author
  • Ji Ho Kim,

    1. SMART Institute of Advanced Biomedical Science, Konkuk University, Seoul, Korea
    2. Department of Biomedical Science and Technology, Research Center for Transcription Control, Konkuk University, Seoul, Korea
    Search for more papers by this author
  • Jung Ho Lee,

    1. SMART Institute of Advanced Biomedical Science, Konkuk University, Seoul, Korea
    Search for more papers by this author
  • Yoongho Lim,

    Corresponding author
    1. Division of Bioscience and Biotechnology, BMIC, Konkuk University, Seoul, Korea
    • SMART Institute of Advanced Biomedical Science, Konkuk University, Seoul, Korea
    Search for more papers by this author
  • Young Han Lee

    Corresponding author
    1. Department of Biomedical Science and Technology, Research Center for Transcription Control, Konkuk University, Seoul, Korea
    • SMART Institute of Advanced Biomedical Science, Konkuk University, Seoul, Korea
    Search for more papers by this author

Correspondence: Professor Young Han Lee, Department of Biomedical Science and Technology, Research Center for Transcription Control, Konkuk University, Seoul 143-701, Korea

E-mail: yhlee58@konkuk.ac.kr

Fax: +82-2-3437-9781

Additional corresponding author: Professor Yoongho Lim

Email: yoongho@konkuk.ac.kr

Abstract

Scope

Natural flavanones exhibit cancer preventive and/or therapeutic effects. The objective of this study was to investigate the molecular mechanism underlying the action of the antitumor activity of hydroxyflavanone using the HCT116 colon cancer cell line.

Methods and results

We investigated the effect of hydroxyflavanones on antitumor activity. We found that 2′-hydroxyflavanone (2′-HF) potently inhibited the clonogenicity of HCT116 cells. 2′-HF triggered apoptosis in both wild-type and p53-null HCT116 cells, as revealed by DNA fragmentation and caspase activation. 2′-HF upregulated nonsteroidal anti-inflammatory drug-activated gene 1 (NAG-1) expression through induction of Egr-1. Silencing of NAG-1 or Egr-1 using small interfering RNA (siRNA) could attenuate 2′-HF-induced apoptosis. Egr-1 also upregulated the proapoptotic gene Bax and the cell cycle inhibitor p21.

Conclusion

Dietary 2′-HF may possess antitumor activity against human colon cancer.

Ancillary