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Research Article

The inhibitory effects of 5-hydroxy-3,6,7,8,3′,4′-hexamethoxyflavone on human colon cancer cells

  1. Peiju Qiu1,2,
  2. Huashi Guan2,
  3. Ping Dong1,
  4. Shanshan Guo1,
  5. Jinkai Zheng1,
  6. Shiming Li3,
  7. Yun Chen4,
  8. Chi-Tang Ho3,
  9. Min-Hsiung Pan5,
  10. David Julian McClements1,
  11. Hang Xiao1,*

Article first published online: 6 JUN 2011

DOI: 10.1002/mnfr.201100070

Issue

Molecular Nutrition & Food Research

Molecular Nutrition & Food Research

Volume 55, Issue 10, pages 1523–1532, October 2011

Additional Information

How to Cite

Qiu, P., Guan, H., Dong, P., Guo, S., Zheng, J., Li, S., Chen, Y., Ho, C.-T., Pan, M.-H., McClements, D. J. and Xiao, H. (2011), The inhibitory effects of 5-hydroxy-3,6,7,8,3′,4′-hexamethoxyflavone on human colon cancer cells. Mol. Nutr. Food Res., 55: 1523–1532. doi: 10.1002/mnfr.201100070

Author Information

  1. 1

    Department of Food Science, University of Massachusetts, Amherst, MA, USA

  2. 2

    Marine Drug and Food Institute, Ocean University of China, Qingdao, Shandong, P. R. China

  3. 3

    Department of Food Science, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA

  4. 4

    Center for Pharmacogenomics, Washington University, St. Louis, MO, USA

  5. 5

    Department of Seafood Science, National Kaohsiung Marine University, Kaohsiung, Taiwan

*Department of Food Science, University of Massachusetts, Amherst, MA, USA Fax: +1-413-545-1262

Publication History

  1. Issue published online: 10 OCT 2011
  2. Article first published online: 6 JUN 2011
  3. Manuscript Accepted: 24 MAR 2011
  4. Manuscript Revised: 16 MAR 2011
  5. Manuscript Received: 30 JAN 2011

Funded by

  • NIH. Grant Number: CA139174
  • American Institute for Cancer Research
  • University of Massachusetts Amherst
  • Pilot Grant from the Center for Excellence in Apoptosis Research at the Pioneer Valley Life Sciences Institute

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Keywords:

  • Angiogenesis;
  • β-Catenin;
  • EGFR;
  • 5-Hydroxy-3,6,7,8,3′,4′-hexamethoxyflavone;
  • K-Ras

Abstract

Scope: Previously, we reported that 5-hydroxy-3,6,7,8,3′,4′-hexamethoxyflavone (5HHMF), a polymethoxyflavone found in citrus peels, potently inhibited the growth of multiple human colon cancer cells. Herein, we further investigated the anti-cancer mechanisms of 5HHMF in human colon cancer cells.

Methods and results: Colony formation assay revealed that 5HHMF dose dependently inhibited colony formation of multiple colon cancer cells. Western blot analysis demonstrated 5HHMF decreased nuclear β-catenin levels and increased the E-cadherin level in a dose-dependent manner. 5HHMF also modified plasma membrane-associated proteins, such as K-Ras, EGFR, and their downstream effectors, such as Akt. Moreover, treatments with 5HHMF inhibited nuclear translocation of NF-κB, which may contribute to its anti-cancer effects. Add-back study showed that the inhibitory effect of 5HHMF was not associated with the production of reactive oxygen species (ROS). In addition, 5HHMF treatment inhibited the capillary tube formation of human umbilical vein endothelial cells (HUVECs) on matrigel, suggesting a potential anti-tumor angiogenesis effect.

Conclusion: Our results demonstrated that 5HHMF suppressed multiple oncogenic molecular events in colon cancer cells.

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