Journal of Cancer Prevention 2016; 21(2): 88-94
Published online June 30, 2016
© Korean Society of Cancer Prevention
Yu Li Kim1,2, Sun Kyoung Lee1, Kwang-Kyun Park1,2, and Won-Yoon Chung1,2
1Department of Oral Biology, Oral Cancer Research Institute, BK21 PLUS Project, Yonsei University College of Dentistry, Seoul, Korea, 2Department of Applied Life Science, The Graduate School, Yonsei University, Seoul, Korea
Correspondence to :
Won-Yoon Chung, Department of Oral Biology, College of Dentistry, Yonsei University, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea, Tel: +82-2-2228-3057, Fax: +82-2-364-7113, E-mail: firstname.lastname@example.org, ORCID: Won-Yoon Chung, http://orcid.org/0000-0001-8428-9005
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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. 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. The fruit and leaf extracts of The extracts of
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.
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.
The fruit and leaf extracts of
The extracts of
Bone metastasis frequently occurs in patients with metastatic breast cancer.1 Bone microenvironment is suitable for breast cancer metastasis because of various growth factors in bone matrix such as insulin-like factors, TGF-β, fibroblast growth factors, platelet-derived growth factors, and bone morphogenetic proteins.2,3 In normal bone, there is balance between osteoclasts which resorb bone and osteoblasts which form bone. Metastatic breast cancer cells secrete osteolytic factors, including parathyroid hormone-related protein, interleukin (IL)-6, IL-8, and IL-11.4 These factors stimulate osteoblasts or stromal cells to produce receptor activator of nuclear factor kappa-B ligand (RANKL) and inhibit decoy receptor osteoprotegerin. RANKL binds to RANK of osteoclasts precursors and induces osteoclast differentiation, causing bone resorption.5,6 The growth factors are released from bone matrix by bone resorption and promote breast cancer cell proliferation and secretion of osteolytic factors.7,8 Therefore, osteoclasts, as well as breast cancer cells, can be a strategic therapeutic target for breast cancer patients with bone metastasis.9,10
Traditional medicine plants are being considered as promising research materials in drug discovery.11
The aim of this study is to evaluate the protective potential of
Four-week old male Institute of Cancer Research (ICR) mice were purchased from the Nara Biotech (Pyeongtaek, Korea). The mice were provided free access to a commercial rodent chow and tap water
Human mammary carcinoma cell line MDA-MB-231 was obtained from the Korea Cell Line Bank (Seoul, Korea) and the cells were maintained in DMEM supplemented with 10% FBS and 1% antibiotic-antimycotic mixture at 37°C. Mouse bone marrow-derived macrophages (BMMs) were isolated from tibiae of 4-week-old male ICR mice and cultured in a α-MEM containing 10% FBS, 30 ng/mL M-CSF, and 1% antibiotic-antimycotic mixture at 37°C. All of the cells were incubated in a humidified atmosphere of 5% CO2.
MDA-MB-231 cells (1 × 103 cells/well) were seeded into a 96-well plate with DMEM containing 10% FBS and the attached cells were incubated in serum-free media with the various concentrations of
Migration assay was performed in 24-well transwell chamber (8 mm pore size; Corning Costar, Cambridge, MA, USA) coated with 10% (w/v) gelatin. Invasion assay was performed using 24-well transwell chamber coated with 10% (w/v) gelatin and 1 mg/mL Matrigel (BD Biosciences, Palo Alto, CA, USA). MDA-MB-231 cells (5 × 104 cells/200 μL) were incubated in serum-free DMEM containing
BMMs (5 × 104 cells/well) were seeded in 96-well plate and cultured with α-MEM containing 10% FBS, M-CSF (30 ng/mL), sRANKL (100 ng/mL), and the various concentrations of
BMMs (5 × 104 cells/well) were seeded in an Osteo assay plate (Corning, Cambridge, MA, USA) and cultured in α-MEM containing 10% FBS, M-CSF (30 ng/mL), and sRANKL (100 ng/mL) for 5 days to induce osteoclastogenesis. The cells were then treated with the various concentrations of
MDA-MB-231 cells (5 × 105 cells/dish) were plated in 60 mm culture dishes and incubated with indicated concentrations of
Data were expressed as mean ± SE of three independent experiments. Statistical analysis was performed with a one-way ANOVA and Student’s
We first investigated the effects of
TGF-β1 plays a critical role in the migration and invasion of breast cancer cells.21,22 MMPs are closely associated with cancer invasion and metastasis.23 The treatment with
Bone loss induced by metastasis of breast cancer is caused by excessive osteoclasts.5 The viability of BMMs as osteoclast precursors was not reduced by the treatment with
In bone mimetic material-coated plates, three
In the present study to investigate whether
In breast cancer patients with bone metastasis, osteoclast formation, and activation were abnormally increased.2 Several enzymes such as cathepsin K and MMPs were released from mature osteoclasts and these hydrolytic enzymes digest organic components of the bone matrix and promote bone resorption.28 Thus, many researchers have paid much attention to osteoclast-targeting new agents for the treatment of patients with bone metastasis of breast cancer.9,10 Recent studies suggest that breast cancer induced-bone destruction can be prevented by controlling RANKL-induced osteoclast formation and activities of these enzymes.20,29-,31 In our study,
This work was carried out with the support of “Cooperative Research Program for Agriculture Science & Technology Development (Project No. PJ011578)” Rural Development Administration, Republic of Korea.
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