• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.6047-6053
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• 2015

Background: Hepatocellular carcinoma is one of the most common cancers worldwide. Its prevalence is increasing in many countries. Plant products can be used to protect against cancer due to natural anticancer and chemopreventive constituents. Strobilanthes crispus is one of plants with potential chemopreventive ability. Objective: This study aimed to evaluate the anticancer effects of Strobilanthes crispus juice on hepatocellular carcinoma cells. Materials and Methods: MTT assays, flow cytometry, comet assays and the reverse transcription-polymerase chain reaction (RT-PCR) were used to determine the effects of juice on DNA damage and cancer cell numbers. Results: This juice induced apoptosis after exposure of the HepG2 cell line for 72 h. High percentages of apoptotic cell death and DNA damage were seen at the juice concentrations above 0.1%. It was found that the juice was not toxic for normal cells. In addition, juice exposure increased the expression level of c-myc gene and reduced the expression level of c-fos and c-erbB2 genes in HepG2 cells. The cytotoxic effects of juice on abnormal cells were in dose dependent. Conclusions: It was concluded that the Strobilanthes crispus juice may have chemopreventive effects on hepatocellular carcinoma cells.

• Journal of Acupuncture Research
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• v.19 no.2
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• pp.78-91
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• 2002

Objective : This study was designed to investigate the anti-cancer effects of bee venom on melanoma in C57BL mice. Materials and Methods : For the induction of melanoma, C57BL mice were treated by DMBA(7, 12-dimethylbenz[a]anthracene). Each group of C57BL mouse was treated with DMBA $50{\mu}g$, $75{\mu}g$, $100{\mu}g$ respectively once a week for 15 weeks. Tumor generation in each group of 10 mice was observed. Cumulative curves were showed in the density and frequency of skin tumor generation. To know the effects of pre-treatment of bee venom on tumor generation by DMBA treatment(frequency of tumor generation), Each group of C57BL mouse was pretreated and treated with bee venom $5{\mu}{\ell}$, $25{\mu}{\ell}$, $50{\mu}{\ell}$ respectively once a week for 3 weeks, whereafter each mouse was treated with DMBA $100{\mu}g$ once a week for 15 weeks. Results and Conclusion (1) There was chemotherapeutic effect, but not chemopreventive effect. (2) Cpp32 activity was increased by $50{\mu}{\ell}$ bee venom treatment. (3) Bee venom treatment inhibited expression of cell-cycle regulating, growth-promoting genes such as c-Jun, c-Fos, and Cyclin Dl, and increased tumor suppressors p53 and p21/Wafl. (4) Bee venom treatment activated expression of a representative apoptosis-inducing gene Bax.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.37 no.1
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• pp.21-29
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• 2011

Introduction: To compare the change in frontal ramal inclination (FRI) in laterognathism after orthognathic surgery. Materials and Methods: Twenty four patients (10 men, 14 women; mean age, $22.8{\pm}5.2$ years) with minimal facial canting (${\leq}$ 2 mm) and apparent menton deviation ($5.9{\pm}2.4\;mm$) who had been operated on to correct facial asymmetry and skeletal CIII malocclusion, were selected. On a preoperative posteroanterior (PA) cephalogram, the FRI of the deviated side and non deviated side, L1 deviation amounts and menton deviation amounts were measured. The FRI differences between both sides were compared, and the correlations between the measured deviated elements and the FRI differences were analyzed. On a postoperative PA cephalogram, the shifting amount of L1, shifting amount of L7 and FRI of both sides were measured, and the correlations between the shifting elements and the change in FRI were analyzed. Results: On the preoperative PA cephalogram, the FRI of the non deviated side was significantly greater than those of the deviated side. The differences in FRI, with a menton deviation amount showed a significant correlation. On the postoperative PA cephalogram, the FRI differences between the deviated and non deviated side were decreased significantly and mandibular transverse movement toward central position was noted. The mean shifting amounts of L7 were associated with the amount of change in the deviated side of FRI. Conclusion: Transverse shifting of the mandible through orthognathic surgery decreases the FRI difference, which showed laterognathism, and improves the facial contour.

• Korean Journal of Poultry Science
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• v.44 no.3
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• pp.199-209
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• 2017

Mitogen-activated protein kinase (MAPK) signaling pathways play a key role in innate immunity, inflammation, cell proliferation, cell differentiation, and cell death. The main objective of this study was to investigate the expression level of candidate MAPK pathway genes in the intestinal mucosal layer of two genetically disparate chicken lines (Marek's disease-resistant line 6.3 and Marek's disease-susceptible line 7.2) induced with necrotic enteritis (NE). Using high-throughput RNA sequencing, we investigated 178 MAPK signaling pathway related genes that were significantly and differentially expressed between the intestinal mucosal layers of the NE-afflicted and control chickens. In total, 15 MAPK pathway genes were further measured by quantitative real-time PCR(qRT-PCR) and the results were consistent with the RNA-sequencing data. All 178 identified genes were annotated through Gene Ontology and mapped onto the KEGG chicken MAPK signaling pathway. Several key genes of the MAPK pathway, ERK1/2, JNK1-3, p38 MAPK, MAP2K1-4, $NF-{\kappa}B1/2$, c-Fos, AP-1, Jun-D, and Jun, were differentially expressed in the two chicken lines. Therefore, we believe that RNA sequencing and qRT-PCR analysis provide resourceful information for future studies on MAPK signaling of genetically disparate chicken lines in response to pathogens.

• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.3
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• pp.613-618
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• 2009

Although the effect of Eucommie umoides oliver in osteoporosis has been studied, direct action of Eucommis ulmoides Oliver on osteoclasts remains unknown. Here we examined whether Eucommiae cortex inhibits osteoclast differentiation and bone resorption, a process known to be involved in bone diseases such as osteoporosis. Water extract from Eucommiae cortex (WE-EC) inhibited differentiation of bone marrow macrophages (BMMs) into osteoclasts without causing cytotoxicity. WE-EC suppressed the phosphorylation of p38, ERK, and JNK in BMMs treated with RANKL. WE EC specifically suppressed the mRNA expression of NFATc1 induced by RANKL. However, WE-EC inhibited stability of c-Fos protein induced by RANKL. Furthermore, WE-EC inhibited osteoclast survival induced by RANKL and in turn suppressed bone resorption. Taken together, our results suggest that WE-EC may be better agents for therapeutic use in bone diseases.

• Biomolecules & Therapeutics
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• v.19 no.1
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• pp.70-76
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• 2011

Bone remodeling is a dynamic process involving a constant balance between osteoclast-induced bone resorption and osteoblast-induced bone formation. Osteoclasts play a crucial homeostatic role in skeletal modeling and remodeling, and destroy bone in many pathological conditions. Previously, we reported that the hexane soluble fraction of Ficus carica inhibited osteoclast differentiation. Poly unsaturated fatty acids, such as ethyl docosahexaenoate (E-DHA), docosahexaenoic acid (DHA), cis-11,14-eicosadienoic acid (EDA) and eicosapentaenoic acid (EPA), were identified from the hexane soluble fraction of Ficus carica. Among them, E-DHA most potently inhibited osteoclastogenesis in RAW264.7 cells. E-DHA reduced the activities of JNK and NF-$\kappa}B$. E-DHA suppressed the expression of c-Fos and nuclear factor of activated T cells c1 (NFATc1). Interestingly, DHA increased the activity of alkaline phosphatase and expression of bone morphogenetic protein 2 (BMP2) more than E-DHA in MC3T3-E1 cells, suggesting that DHA may induce osteoblast differentiation. The data suggests that a combination of E-DHA and DHA has potential use in the treatment of diseases involving abnormal bone lysis, such as osteoporosis, rheumatoid arthritis and periodontal bone erosion.

• Biomolecules & Therapeutics
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• v.28 no.4
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• pp.337-343
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• 2020

Activation of osteoclast and inactivation of osteoblast result in loss of bone mass with bone resorption, leading to the pathological progression of osteoporosis. The receptor activator of NF-κB ligand (RANKL) is a member of the TNF superfamily, and is a key mediator of osteoclast differentiation. A flavanone glycoside isolated from the fruit of Poncirus trifoliata, poncirin has anti-allergic, hypocholesterolemic, anti-inflammatory and anti-platelet activities. The present study investigates the effect of poncirin on osteoclast differentiation of RANKL-stimulated RAW264.7 cells. We observed reduced formation of RANKL-stimulated TRAP-positive multinucleated cells (a morphological feature of osteoclasts) after poncirin exposure. Real-time qPCR analysis showed suppression of the RANKL-mediated induction of key osteoclastogenic molecules such as NFATc1, TRAP, c-Fos, MMP9 and cathepsin K after poncirin treatment. Poncirin also inhibited the RANKL-mediated activation of NF-κB and, notably, JNK, without changes in ERK and p38 expression in RAW264.7 cells. Furthermore, we assessed the in vivo efficacy of poncirin in the lipopolysaccharide (LPS)-induced bone erosion model. Evaluating the micro-CT of femurs revealed that bone erosion in poncirin treated mice was markedly attenuated. Our results indicate that poncirin exerts anti-osteoclastic effects in vitro and in vivo by suppressing osteoclast differentiation. We believe that poncirin is a promising candidate for inflammatory bone loss therapeutics.

• Natural Product Sciences
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• v.24 no.1
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• pp.21-27
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• 2018

Psoriasis is an auto-immune skin disease, which is characterized by the excessive generation of plaques on the skin with typically a long-lasting red, itchy and scaly symptoms. Imiquimod, which has been used for the treatment of external genital warts, actinic keratosis, and superficial basal cell carcinoma, induced of psoriasis-like skin disorders with skin erythema and thickness in mice. In the present study, we tried to find the bioactive herbal extract against imiquimod-induced psoriasis-like skin disorder in mice. During the searching of the herbal extract with anti-psoriatic effect, the ethanolic extract of Cnidium officinale ameliorated imiquimod-induced psoriasis-like skin disorder in mice. The morphological evaluation, H&E staining and Psoriasis Area and Severity Index (PASI) score showed that ear and back thickness, and erythema induced by imiquimod were significantly reversed after the treatment of the cream of the ethanolic extract of C. officinale. The overexpressed myeloperoxidase (MPO) and keratin 6A levels were decreased by the treatment of C. officinale cream. Also, $IFN-{\gamma}$, c-fos and $I{\kappa}B-{\alpha}$ mRNA levels, which are related to the progression of psoriasis, were reduced by C. officinale cream. Thus, the ethanolic extract of C. officinale ameliorated psoriasis-like skin disorder induced by imiquimod and might be the therapeutic agent for psoriasis.

• Molecules and Cells
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• v.40 no.10
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• pp.706-713
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• 2017

Osteoclasts are bone-resorbing cells that are derived from hematopoietic precursor cells and require macrophage-colony stimulating factor and receptor activator of nuclear factor-${\kappa}B$ ligand (RANKL) for their survival, proliferation, differentiation, and activation. The binding of RANKL to its receptor RANK triggers osteoclast precursors to differentiate into osteoclasts. This process depends on RANKL-RANK signaling, which is temporally regulated by various adaptor proteins and kinases. Here we summarize the current understanding of the mechanisms that regulate RANK signaling during osteoclastogenesis. In the early stage, RANK signaling is mediated by recruiting adaptor molecules such as tumor necrosis factor receptorassociated factor 6 (TRAF6), which leads to the activation of mitogen-activated protein kinases (MAPKs), and the transcription factors nuclear factor-${\kappa}B$ (NF-${\kappa}B$) and activator protein-1 (AP-1). Activated NF-${\kappa}B$ induces the nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), which is the key osteoclastogenesis regulator. In the intermediate stage of signaling, the co-stimulatory signal induces $Ca^{2+}$ oscillation via activated phospholipase $C{\gamma}2$ ($PLC{\gamma}2$) together with c-Fos/AP-1, wherein $Ca^{2+}$ signaling facilitates the robust production of NFATc1. In the late stage of osteoclastogenesis, NFATc1 translocates into the nucleus where it induces numerous osteoclast-specific target genes that are responsible for cell fusion and function.

• Molecules and Cells
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• v.40 no.10
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• pp.752-760
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• 2017

A2B adenosine receptor (A2BAR) is known to be the regulator of bone homeostasis, but its regulatory mechanisms in osteoclast formation are less well-defined. Here, we demonstrate the effect of A2BAR stimulation on osteoclast differentiation and activity by RANKL. A2BAR was expressed in bone marrow-derived monocyte/macrophage (BMM) and RANKL increased A2BAR expression during osteoclastogenesis. A2BAR stimulation with its specific agonist BAY 60-6583 was sufficient to inhibit the activation of ERK1/2, p38 MAP kinases and $NF-{\kappa}B$ by RANKL as well as it abrogated cell-cell fusion in the late stage of osteoclast differentiation. Stimulation of A2BAR suppressed the expression of osteoclast marker genes, such as c-Fos, TRAP, Cathepsin-K and NFATc1, induced by RANKL, and transcriptional activity of NFATc1 was also inhibited by stimulation of A2BAR. A2BAR stimulation caused a notable reduction in the expression of Atp6v0d2 and DC-STAMP related to cell-cell fusion of osteoclasts. Especially, a decrease in bone resorption activity through suppression of actin ring formation by A2BAR stimulation was observed. Taken together, these results suggest that A2BAR stimulation inhibits the activation of ERK1/2, p38 and $NF-{\kappa}B$ by RANKL, which suppresses the induction of osteoclast marker genes, thus contributing to the decrease in osteoclast cell-cell fusion and bone resorption activity.