Halofuginone induces the apoptosis of breast cancer cells and inhibits migration via downregulation of matrix metalloproteinase-9

Jin,Mei   Ling; Park,Sun  Young; Kim,Young   Hun; Park,Geuntae; Lee,Sang  Joon

doi:10.3892/ijo.2013.2157

Halofuginone induces the apoptosis of breast cancer cells and inhibits migration via downregulation of matrix metalloproteinase-9

Authors:
- Mei Ling Jin
- Sun Young Park
- Young Hun Kim
- Geuntae Park
- Sang Joon Lee
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Affiliations: Department of Microbiology, Pusan National University, Busan 609-735, Republic of Korea, Bio-IT Fusion Technology Research Institute, Pusan National University, Busan 609-735, Republic of Korea, Institute for Research and Industry Cooperation, Pusan National University, Busan 609-735, Republic of Korea
Published online on: October 31, 2013 https://doi.org/10.3892/ijo.2013.2157
Pages: 309-318

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Abstract

Halofuginone (HF) is extracted from Dichroa febrifuga, a plant used in traditional medicine. We report that the HF extract inhibits the growth of breast cancer cells and induces the generation of reactive oxygen species (ROS) and apoptosis, an important feature of potential anticancer agents. In addition, HF significantly reduces the migration and invasion of MCF-7 and MDA-MB-231 human breast cancer cells after 12-O-tetraecanoylphorbol-13-acetate (TPA) stimulation. As matrix metalloproteinase-9 plays a critical role in tumor metastasis, we analyzed its expression with the HF extract treatment. Western blot analysis and gelatin zymography showed that HF suppresses MMP-9 expression and activity concentration-dependently. HF also decreases the nuclear protein levels of nuclear factor kappa B (NF-κB) and c-fos (AP-1), critical transcription factors regulating MMP-9 expression through binding the MMP-9 promoter region. Luciferase assays showed that HF decreases TPA-induced MMP-9 promoter binding activities of NF-κB and AP-1. Taken together, these are the first results indicating that halofuginone may represent a promising new agent for breast cancer chemotherapy.

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