• Asian Pacific Journal of Cancer Prevention
• /
• v.17 no.7
• /
• pp.3627-3629
• /
• 2016

Background: Activation and inactivation of nuclear factor of kappa light chain gene enhancer in B cells (NFKB) is tightly regulated to ensure effective onset and cessation of defensive inflammatory signaling. However, mutations within NFKB, or change in activation and inactivation molecules have been reported in a few cancers. Although oral squamous cell carcinoma is one of the most prevalent forms of cancer in India, with a development associated with malignant transformation of precancerous lesions, the genetic status of NFKB and relative rates of change in oral precancerous lesions remain unknown. Hence in the present study we investigated all twenty four exons of NFKB gene in two precancerous lesions, namely oral submucous fibrosis (OSMF) and oral leukoplakia (OL) to understand its occurrence, incidence and assess its possible contribution to malignant transformation. Materials and Methods: Chromosomal DNA isolated from twenty five each of OSMF and OL tissue biopsy samples were subjected to PCR amplification with intronic primers flanking twenty four exons of the NFKB gene. The PCR amplicons were subsequently subjected to direct sequencing to elucidate the mutation status. Results: Sequence analysis identified a novel heterozygous mutation, c.419T>A causing substitution of leucine with glutamine at codon 140 (L140Q) in an OL sample. Conclusions: The identification of a substitution mutation L140Q within the DNA binding domain of NFKB in OL suggests that NFKB mutation may be relatively an early event during transformation. To the best of our knowledge, this study is the first to have identified a missense mutation in NFKB in OL.

• Molecules and Cells
• /
• v.39 no.10
• /
• pp.742-749
• /
• 2016

The cancer chemo-preventive effects of equol have been demonstrated for a wide variety of experimental tumours. In a previous study, we found that equol inhibited proliferation and induced apoptotic death of human gastric cancer MGC-803 cells. However, the mechanisms underlying equol-mediated apoptosis have not been well understood. In the present study, the dual AO (acridine orange)/EB (ethidium bromide) fluorescent assay, the comet assay, MTS, western blotting and flow cytometric assays were performed to further investigate the pro-apoptotic effect of equol and its associated mechanisms in MGC-803 cells. The results demonstrated that equol induced an apoptotic nuclear morphology revealed by AO/EB staining, the presence of a comet tail, the cleavage of caspase-3 and PARP and the depletion of cIAP1, indicating its pro-apoptotic effect. In addition, equol-induced apoptosis involves the mitochondria-dependent cell-death pathway, evidenced by the depolarization of the mitochondrial membrane potential, the cleavage of caspase-9 and the depletion of Bcl-xL and full-length Bid. Moreover, treating MGC-803 cells with equol induced the sustained activation of extracellular signal-regulated kinase (ERK), and inhibiting ERK by U0126, a MEK/ERK pathway inhibitor, significantly attenuated the equol-induced cell apoptosis. These results suggest that equol induces mitochondria-dependent apoptosis in human gastric cancer MGC-803 cells via the sustained activation of the ERK1/2 pathway. Therefore, equol may be a novel candidate for the chemoprevention and therapy of gastric cancer.

• KSBB Journal
• /
• v.29 no.1
• /
• pp.50-57
• /
• 2014

NF-${\kappa}B$ is a transcriptional factor which is involved in many biological processes including immunity, inflammation, and cell survival. Many investigators studied on the mechanism involved in activation of NF-${\kappa}B$ signalling pathway via ubiquitination and degradation of $I{\kappa}B$ regarding skin disease. Some specific molecules including Akt, MEK, p38 MAP Kinase, Stat3, et al. represent convergence points and key regulatory proteins in signaling pathways controlling cellular events such as growth and differentiation, energy homeostasis, and the response to stress and inflammation. Ultraviolet (UV) irradiation has many adverse effects on skin, including inflammation, alteration in the extracellular matrix, cellular senescence, apoptosis and skin cancer. Prunus mume, a naturally derived plant extract, has beneficial biological activities as blood fluidity improvement, anti-fatigue action, antioxidative and free radical scavenging activities, inhibiting the motility of Helicobacter pyolri. Previous reports on various beneficial function prompted us to investigate UVB-induced or other immunostimulated biological marker regarding P. mume extract. P. mume extract suppresses UVB-induced cyclooxygenase-2 (COX-2) expression in mouse skin epidermal JB6 P+ cells. The activation of activator protein-1 and nuclear factor-${\kappa}B$ induced by UVB was dose-dependently inhibited by P. mume extract treatment. This results suggest that P. mume extracts might be used as a potential agents for protection of inflammation or UVB induced skin damage.

• IMMUNE NETWORK
• /
• v.14 no.3
• /
• pp.138-148
• /
• 2014

MicroRNAs (miRNAs) are endogenous small RNA molecules best known for their function in post-transcriptional gene regulation. Immunologically, miRNA regulates the differentiation and function of immune cells and its malfunction contributes to the development of various autoimmune diseases including systemic lupus erythematosus (SLE). Over the last decade, accumulating researches provide evidence for the connection between dysregulated miRNA network and autoimmunity. Interruption of miRNA biogenesis machinery contributes to the abnormal T and B cell development and particularly a reduced suppressive function of regulatory T cells, leading to systemic autoimmune diseases. Additionally, multiple factors under autoimmune conditions interfere with miRNA generation via key miRNA processing enzymes, thus further skewing the miRNA expression profile. Indeed, several independent miRNA profiling studies reported significant differences between SLE patients and healthy controls. Despite the lack of a consistent expression pattern on individual dysregulated miRNAs in SLE among these studies, the aberrant expression of distinct groups of miRNAs causes overlapping functional outcomes including perturbed type I interferon signalling cascade, DNA hypomethylation and hyperactivation of T and B cells. The impact of specific miRNA-mediated regulation on function of major immune cells in lupus is also discussed. Although research on the clinical application of miRNAs is still immature, through an integrated approach with advances in next generation sequencing, novel tools in bioinformatics database analysis and new in vitro and in vivo models for functional evaluation, the diagnostic and therapeutic potentials of miRNAs may bring to fruition in the future.

• Molecules and Cells
• /
• v.43 no.9
• /
• pp.793-803
• /
• 2020

Myeloid-derived suppressor cells (MDSCs) promote tumour progression by contributing to angiogenesis, immunosuppression, and immunotherapy resistance. Although recent studies have shown that microRNAs (miRNAs) can promote the expansion of MDSCs in the tumour environment, the mechanisms involved in this process are largely unknown. Here, we report that microRNA 449c (miR-449c) expression was upregulated in myeloid progenitor cells upon activation of C-X-C motif chemokine receptor 2 (CXCR2) under tumour conditions. MiR-449c upregulation increased the generation of monocytic MDSCs (mo-MDSCs). The increased expression of miR-449c could target STAT6 mRNA in myeloid progenitor cells to shift the differentiation balance of myeloid progenitor cells and lead to an enhancement of the mo-MDSCs population in the tumour environment. Thus, our results demonstrate that the miR-449c/STAT6 axis is involved in the expansion of mo-MDSCs from myeloid progenitor cells upon activation of CXCR2, and thus, inhibition of miR-449c/STAT6 signalling may help to attenuate tumour progression.

• Korean Journal of Head & Neck Oncology
• /
• v.21 no.1
• /
• pp.15-20
• /
• 2005

Objectives: The hepatocyte growth factor(HGF)/c-Met pathway may play various roles in the carcinogenesis of various organs. Although HGF/c-Met signalling pathway has been shown to demonstrate various cellular responses including mitogenic, proliferative, morphogenic and angiogenic activities, the study on their expression related to clinicopathological parameters in thyroid tumor is relatively rare. So we want to find out the clinical significance of the c-Met in thyroid tumor. Materials and Methods: We assess the mRNA and protein expression of the c-Met genes by means of RT-PCR method and the immunohistochemical stain in 100 cases of thyroid tumors(50 papillary carcinomas, 10 follicular carcinomas, 20 follicular adenomas, 20 nodular hyperplasia). Results: By RT-PCR, c-Met mRNA was detected in 43(86%) in papillary carcinoma, 4(40%) in follicular carcinoma, 4(20%) in follicular adenoma and 2(10%) in nodular hyperplasia cases. By immunohistochemistry, c-Met protein expression was detected in 44(88%), 2(20%), 3(15%) and 1(5%). Expression of the c-Met mRNA and protein expression was significantly highly recognized in papillary carcinoma. The c-Met protein overexpression was significantly correlated with the grade of the differentiation. Conclusion: These results suggest that c-Met expression may be associated with thyroid papillary cancer progression. The differential expression of c-Met protein and mRNA suggests that these molecules may be a reliable diagnostic marker in thyroid papillary cancer.

• Journal of Microbiology and Biotechnology
• /
• v.29 no.5
• /
• pp.827-837
• /
• 2019

The present study was conducted with the aim to investigate the ameliorative effects of a new soybean product (cheonggukjang) fermented with Bacillus amyloliquefaciens SCGB1 (SFBA) in atopic dermatitis (AD) mouse model. Visual evaluation of AD induction in the mice indicated the remarkable control of SFBA in reducing the pathological severity of AD-like skin lesions reported as the SCORAD score of AD clinical symptoms. The results revealed that SFBA reduced dorsal skin and epidermal thickness to a similar extent with prednisolone. Further analysis revealed the dominance of SFBA in restraining mast cell infiltration in the dermis; immunoglobulin-E expression in serum; and TH2 IL-4 cytokine and itch-related IL-31 cytokine in the mice skin and serum. SFBA also suppressed scratching behaviours in mice induced by compound 48/80. Further histological findings also revealed the alleviation of collagen fiber deposition in dermal skin of the AD mice model. These actions of SFBA were examined to be mediated by its suppression of the phosphorylation activation of key signalling molecules such as $NF-{\kappa}B$ and MAPK responsible for the induction of cytokine production. Thus, SFBA can be considered as a promising functional food for managing clinical, histological and immunological spectra associated with AD.

• The Journal of Korean Obstetrics and Gynecology
• /
• v.22 no.3
• /
• pp.117-134
• /
• 2009

Purpose: In the theory of traditional medicine, Scutellariae Radix (SR) can clear away heat and remove dampness, purge the sthenic fire and remove toxic materials, cool blood and stop bleeding to prevent miscarriage. Recently, SR is known to have anti-cancer activity. For this reason, the present author designed to investigate the effect of SR on proliferation rates of cervical cancer cell line, then effects on genetic profile by SR. Methods: The genetic profile for the effect of SR on human derived cervical cancer cell line, SNU-703, was measured using microarray technique, and the functional analysis on these genes was conducted. Results: Total 519 genes were up-regulated and 606 genes down-regulated in cells treated with SR. Genes induced or suppressed by SR were all mainly concerned with metabolic process, regulation of biological process and protein binding. The network of total protein interactions was measured using cytoscape program, and some key molecules, such as TNFRSF1A, AKT1, MAPK3, and STAT3 that can be used for elucidation of therapeutical mechanism of medicine in future were identified. Conclusion: These results suggest possibility of SR as anti-cancer drug and also suggest that related mechanisms are involved in TNFRSF1A, AKT1, MAPK3, and STAT3 related signalling pathways.

• Molecules and Cells
• /
• v.40 no.3
• /
• pp.222-229
• /
• 2017

Adipose-derived stem cells (ADSCs) were previously considered to have an anti-inflammatory effect, and Interleukin-$1{\beta}$ ($IL-1{\beta}$) was found to be a pro-inflammatory factor in chondrocytes, but the mechanism underlying ADSCs and $IL-1{\beta}$ is unclear. In this study, we investigate whether P2X7 receptor (P2X7R) signalling, regulated by microRNA 373 (miR-373), was involved in the ADSCs and $IL-1{\beta}$ mediated inflammation in osteoarthritis (OA). Chondrocytes were collected from 20 OA patients and 20 control participants, and ADSCs were collected from patients who had undergone abdominal surgery. The typical surface molecules of ASDCs were detected by flow cytometry. The level of nitric oxide (NO) was determined by Griess reagent. Concentrations of prostaglandin E2 (PGE2), interleukin 6 (IL-6), matrix metallopeptidase 3 (MMP-3) were detected by enzyme-linked immunosorbent assay (ELISA). The expressions of IL-6, MMP-3, miR-373 and P2X7R were determined by real-time polymerase chain reaction (PCR), and Western blot was used to detect the protein expression of P2X7R. The typical potential characters of ADSCs were verified. In chondrocytes or OA tissues, the miR-373 expression level was decreased, but the P2X7R expression was increased. $IL-1{\beta}$ stimulation increased the level of inflammatory factors in OA chondrocytes, and ADSCs co-cultured with $IL-1{\beta}$-stimulated chondrocytes decreased the inflammation. OA chondrocytes transfected with the miR-373 inhibitor increased the inflammation level. The miR-373 mimic suppressed the inflammation by targeting P2X7R and regulated its expression, while its effect was reversed by overexpression of P2X7R. $IL-1{\beta}$ induced inflammation in OA chondrocytes, while ADSCs seemed to inhibit the expression of P2X7R that was regulated by miR-373 and involved in the anti-inflammatory process in OA.

• Applied Biological Chemistry
• /
• v.48 no.1
• /
• pp.53-59
• /
• 2005

The effect of various stressors such as reductant ascorbic acid, signalling molecules (salicylic acid and methyl jasmonic acid), heavy metals $(NiCl_2,\;and\;MnSO_4)$ and NaCl on the glutathione peroxidase (GPX) activities and isoenzyme expression patterns were investigated in rice seedling roots. Total GPX activity increased according to the increase of ascorbic acid concentration. Prominent enhancement of GPX1 isozyme due to ascorbic acid contributed to the increase of total GPX activity. GPX showed different reactivity toward salicylic acid and methyl jasmonic acid. GPX activity increased at 0.1 mM salicylic acid, and then decreased thereafter. However, GPX increased gradually in a methyl jasmonic acid concentration-dependent manner, and 3 fold increase of GPX activity was found at 1 mM methyl jasmonic acid. Moreover, GPX1 isozyme increased according to the increase of salicylic acid, while GPX1 isozyme decreased according to the increase of methyl jasmonic acid. When metal ions were treated, GPX activity increased considerably according to the increase of $NiCl_2$ concentration, however, GPX activity increased about 2 fold at 0.5 mM $CuSO_4$ and then decreased. Enhancement of GPX1 isozyme contributed to the increase of total GPX activities in $NiCl_2-treated$ and $MnSO_4-treated$ rice seedlings. Total GPX activity increased 1.7 fold in response to 300 mM NaCl. Especially GPX2 isozyme showed gradual increase according to the increase of NaCl concentration.