J Cancer Prev.  2016 Jun;21(2):88-94. 10.15430/JCP.2016.21.2.88.

The Inhibitory Effects of Forsythia Koreana Extracts on the Metastatic Ability of Breast Cancer Cells and Bone Resorption by Osteoclasts

• Kim YL
• Lee SK
• Park KK
• Chung WY

• KMID: 2353808
• DOI: http://doi.org/10.15430/JCP.2016.21.2.88

Abstract

BACKGROUND
Breast cancer is the most common malignant disease in women. The patients with advanced breast cancer develop metastasis to bone. Bone metastasis and skeletal-related events by breast cancer are frequently associated with the invasiveness of breast cancer cells and osteoclasts-mediated bone resorption. Forsythia koreana is used in oriental traditional medicine to treat asthma, atopy, and allergic diseases. The aim of this study was to evaluate the inhibitory effects of F. koreana extracts on the invasion of breast cancer cells and bone resorption by osteoclasts.
METHODS
Cell viability was measured by an MTT assay and the migration and invasion of MDA-MB-231 cells were detected by a Boyden chamber assay. The formation of osteoclasts and pit was detected using tartrate-resistant acid phosphatase staining and calcium phosphate-coated plates, respectively. The activities of matrix metalloproteinases (MMPs) and cathepsin K were evaluated by gelatin zymography and a cathepsin K detection kit.
RESULTS
The fruit and leaf extracts of F. koreana significantly inhibited the invasion of MDA-MB-231 cells at noncytotoxic concentrations. The fruit extract of F. koreana reduced the transforming growth factor β1-induced migration, invasion and MMPs activities of MDA-MB-231 cells. In addition, the fruit, branch, and leaf extracts of F. koreana also inhibited the receptor activator of nuclear factor kappa-B ligand-induced osteoclast formation and osteoclast-mediated bone-resorbing activity by reducing the activities of MMPs and cathepsin K.
CONCLUSIONS
The extracts of F. koreana may possess the potential to inhibit the breast cancer-induced bone destruction through blocking invasion of breast cancer cells, osteoclastogenesis, and the activity of mature osteoclasts.

Keyword

Forsythia koreana; Breast neoplasm; Bone metastasis; Osteoclast; Bone resorption

MeSH Terms

Acid Phosphatase
Asthma
Bone Resorption*
Breast Neoplasms*
Breast*
Calcium
Cathepsin K
Cell Survival
Female
Forsythia*
Fruit
Gelatin
Humans
Matrix Metalloproteinases
Medicine, East Asian Traditional
Neoplasm Metastasis
Osteoclasts*
Transforming Growth Factors
Acid Phosphatase
Calcium
Cathepsin K
Gelatin
Matrix Metalloproteinases
Transforming Growth Factors