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

Cited by 46 publications

(33 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…One recent study demonstrated that halofuginone could reduce tumor growth [31]. However, in our in vivo study halofuginone alone cannot significantly reduce tumor growth, but combination treatment with radiation and halofuginone caused significant inhibition of tumor growth compared to halofuginone or radiation alone.…”

Section: Discussioncontrasting

confidence: 56%

Halofuginone inhibits radiotherapy-induced epithelial-mesenchymal transition in lung cancer

et al. 2016

View full text Add to dashboard Cite

Radiotherapy is used to treat many different human tumors. Paradoxically, radiation can activate TGF-β1 signaling and induce the epithelial-mesenchymal transition (EMT), which is associated with enhanced tumor progression. This study investigated the inhibitory effects of halofuginone, a plant-derived alkaloid that has been shown to inhibit TGF-β1 signaling, on radiation-induced EMT and explored the underlying mechanisms using a Lewis lung carcinoma (LLC) xenograft model. The cells and animals were divided into five treatment groups: Normal Control (NC), Halofuginone alone (HF), Radiotherapy alone (RT), Radiotherapy combined with Halofuginone (RT+HF), and Radiotherapy combined with the TGF-β1 inhibitor SB431542 (RT+SB). Radiation induced EMT in lung cancer cells and xenografts, as evidenced by increased expression of the mesenchymal markers N-cadherin and Vimentin, and reduced expression of the epithelial markers E-cadherin and Cytokeratin. Further, radiotherapy treatment increased the migration and invasion of LLC cells. Halofuginone reversed the EMT induced by radiotherapy in vitro and in vivo, and inhibited the migration and invasion of LLC cells. In addition, TGF-β1/Smad signaling was activated by radiotherapy and the mRNA expression of Twist and Snail was elevated; this effect was reversed by halofuginone or the TGF-β1 inhibitor SB431542. Our results demonstrate that halofuginone inhibits radiation-induced EMT, and suggest that suppression of TGF-β1 signaling may be responsible for this effect.

show abstract

Section: Discussioncontrasting

confidence: 56%

Halofuginone inhibits radiotherapy-induced epithelial-mesenchymal transition in lung cancer

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Like all other types of solid tumors, breast cancer is a refractory disease. Although there are tremendous amount of cancer‐fighting drugs, including chemical drugs, which have low efficacy and inherent degree of toxicity, and may result in acquired drug resistance (Jin, Park, Kim, Park, & Lee, ). Therefore, clinicians must perennially to explore new, less toxicity and more effectual therapeutic molecules for cancer treatment.…”

Section: Introductionmentioning

confidence: 99%

miR‐31 shuttled by halofuginone‐induced exosomes suppresses MFC‐7 cell proliferation by modulating the HDAC2/cell cycle signaling axis

Xia

Wang

Zhang

et al. 2019

Journal Cellular Physiology

View full text Add to dashboard Cite

Traditional Chinese medicine (TCM) are both historically important therapeutic agents and important source of new drugs. Halofuginone (HF), a small molecule alkaloid derived from febrifugine, has been shown to exert strong antiproliferative effects that differ markedly among various cell lines. However, whether HF inhibits MCF‐7 cell growth in vitro and underlying mechanisms of this process are not yet clear. Here, we offer the strong evidence of the connection between HF treatment, exosome production and proliferation of MCF‐7 cells. Our results showed that HF inhibits MCF‐7 cell growth in both time‐ and dose‐dependent manner. Further microRNA (miRNA) proﬁles analysis in HF treated and nontreated MCF‐7 cell and exosomes observed that six miRNAs are particularly abundant and sorted in exosomes. miRNAs knockdown experiment in exosomes and the MCF‐7 growth inhibition assay showed that exosomal microRNA‐31 (miR‐31) modulates MCF‐7 cells growth by specially targeting the histone deacetylase 2 (HDAC2), which increases the levels of cyclin‐dependent kinases 2 (CDK2) and cyclin D1 and suppresses the expression of p21. In conclusion, these data indicate that inhibition of exosome production reduces exosomal miR‐31, which targets the HDAC2 and further regulates the level of cell cycle regulatory proteins, contributing to the anticancer functions of HF. Our data suggest a new role for HF and the exosome production in tumorigenesis and may provide novel insights into prevention and treatment of breast cancer.

show abstract

“…A previous study reported that oroxylin A could inhibit migration and invasion of human breast MDA-MB-435 cancer cells via the inhibition of MMP-2 and MMP-9 (11). Thus, MMP-2 and MMP-9 have been considered as targets in the development of drugs against tumor invasion and metastasis (12,13).…”

Section: Introductionmentioning

confidence: 98%

Ophiopogonin-D suppresses MDA-MB-435 cell adhesion and invasion by inhibiting matrix metalloproteinase-9

Zhang

Han

Zhai

et al. 2012

Molecular Medicine Reports

View full text Add to dashboard Cite

Ophiopogonin-D is one of steroidal saponins isolated from the root of the Chinese medicinal plant Ophiopogon japonicas. It has been claimed to possess anti-inflammatory and anti-oxidant properties. The present study was the first to examine the anti-tumor metastasis properties of ophiopogonin-D. An MTT assay showed that ophiopogonin-D inhibited the proliferation of MDA-MB-435 melanoma cells, and decreased invasion was demonstrated using a Transwell invasion assay. Furthermore, adhesion of MDA-MB-435 cells to human umbilical vascular endothelial cells and to fibronectin was inhibited by ophiopogonin-D. Gelatin zymography and western blot analysis showed that ophiopogonin-D inhibited the expression and secretion of matrix metalloproteinase-9 (MMP-9), but not that of MMP-2. Inhibition of phosphorylation of p38 by ophiopogonin-D indicated its inhibition of the mitogen-activated protein kinase pathway. Overall, the results suggested that ophiopogonin-D may be considered as a candidate drug for treating or preventing tumor metastasis.

show abstract

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

Cited by 46 publications

References 36 publications

Halofuginone inhibits radiotherapy-induced epithelial-mesenchymal transition in lung cancer

Halofuginone inhibits radiotherapy-induced epithelial-mesenchymal transition in lung cancer

miR‐31 shuttled by halofuginone‐induced exosomes suppresses MFC‐7 cell proliferation by modulating the HDAC2/cell cycle signaling axis

Ophiopogonin-D suppresses MDA-MB-435 cell adhesion and invasion by inhibiting matrix metalloproteinase-9

Contact Info

Product

Resources

About