• Journal of Microbiology and Biotechnology
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• v.29 no.10
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• pp.1675-1681
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• 2019

Clostridium difficile toxin A is known to cause colonic epithelial cell apoptosis, which is considered the main causative event that triggers inflammatory responses in the colon, reflecting the concept that the essential role of epithelial cells in the colon is to form a physical barrier in the gut. We previously showed that toxin A-induced colonocyte apoptosis and subsequent inflammation were dependent on prostaglandin E2 ($PGE_2$) produced in response to toxin A stimulation. However, the molecular mechanism by which $PGE_2$ mediates cell apoptosis in toxin A-exposed colonocytes has remained unclear. Here, we sought to identify the signaling pathway involved in toxin A-induced, $PGE_2$-mediated colonocyte apoptosis. In non-transformed NCM460 human colonocytes, toxin A exposure strongly upregulated expression of Bak, which is known to form mitochondrial outer membrane pores, resulting in apoptosis. RT-PCR analyses revealed that this increase in Bak expression was attributable to toxin A-induced transcriptional upregulation. We also found that toxin A upregulation of Bak expression was dependent on $PGE_2$ production, and further showed that this effect was recapitulated by an Prostaglandin E2(PGE2) receptor-1 receptor agonist, but not by agonists of other EP receptors. Collectively, these results suggest that toxin A-induced cell apoptosis involves $PGE_2$-upregulation of Bak through the EP1 receptor.

• Journal of Soil and Groundwater Environment
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• v.12 no.1
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• pp.97-102
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• 2007

An environmental survey from three abandoned metal mine areas was undertaken on to assess the risk of adverse health effects on human exposure to heavy metals influenced by past mining activities. Tailings contained high concentrations of heavy metals may have a impact on soils and waters around the tailing piles. In order to perform the human risk assessment, chemical analysis data of soils, rice grains and waters for As, Cd, Cu and Pb have been used. The HQ values for heavy metals via the rice consumption were significantly higher compared with other exposure pathways in all metal mine areas. The resulting HI values in three mine areas were higher than 9.0, and their toxic risk due to rice ingestion was strong in these mine areas. The cancer risk of being exposed to As by the rice consumption from the A, B and C mine areas was $5.1\;{\times}\;10^{-3}$, $6.8\;{\times}\;10^{-3}$ and $3.1\;{\times}\;10^{-3}$, respectively. The As cancer risk via the exposure pathway of rice ingestion from these mine areas exceeds the acceptable risk of 1 in 10,000 set for regulatory purposes. Thus, the daily intakes of rice by the local residents from these mine areas can pose a potential health threat if exposed by long-term As exposure.

• Genomics & Informatics
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• v.8 no.1
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• pp.28-33
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• 2010

Increased exposure of human to RF fields has raised concerns for its potential adverse effects on our health. To address the biological effects of RF radiation, we used genome wide gene expression as the indicator. We exposed normal WI-38 human fibroblast cells to 1763 MHz mobile phone RF radiation at a specific absorption rate (SAR) of 60 W/kg with an operating cooling system for 24 h. There were no alterations in cell numbers or morphology after RF exposure. Through microarray analysis, we identified no differentially expressed genes (DEGs) at the 0.05 significance level after controlling for multiple testing errors with the Benjaminiochberg false discovery rate (BH FDR) method. Meanwhile, 82 genes were differentially expressed between RF-exposed cells and controls when the significance level was set at 0.01 without correction for multiple comparisons. We found that 24 genes (0.08% of the total genes examined) were changed by more than 1.5-fold on RF exposure. However, significant enrichment of any gene set or pathway was not observed from the functional annotation analysis. From these results, we did not find any evidence that non-thermal RF radiation at a 60-W/kg SAR significantly affects cell proliferation or gene expression in WI-38 cells.

• Journal of Soil and Groundwater Environment
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• v.21 no.6
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• pp.56-66
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• 2016

Generally, the contribution of crop-intake pathway (CIP) is remarkable in human health assessment (HHA) of heavy metal contamination. Although the crop exposure concentrations (Cp) should directly be used for calculating the average daily dose (ADD) of CIP, the soil exposure concentration (Cs) multiplied by soil-crop bio-concentration factor (BCF) has frequently been used instead of using Cp values. Thus, the BCF values are significant in the HHA, and care should be taken to ensure the reasonable acquisition of BCF values. Meanwhile, the BCF values are known to be significantly affected by analytical methods. Nevertheless, they have been calculated from the concentrations of soil and crop analyzed by only one method: total digestion (aqua regia extraction). For this reason, this study was initiated to seek appropriate soil analysis methods for effective computation of the ADD of CIP. The concentrations of 5 metal contaminants (As, Cd, Cu, Pb, and Zn) in 127 soil samples obtained from 4 abandoned metal mine areas were analyzed by several methods including total digestion and partial digestions using 0.1/1 N HCl, 1M $NH_4NO_3$, 0.1 M $NaNO_3$, and 0.01M $CaCl_2$. The heavy metal concentrations in 127 crop samples (rice grains) were analyzed by total digestion as well. Using the concentrations of soils and crops, the BCF values of each contaminant were calculated according to the kind of soil extraction methods applied. Finally, the errors between Cp and $C_s{\times}BCF$ were computed to evaluate the relevance of each method. The results indicate that the partial extraction using 0.1 N and 1 N HCl was superior or equivalent to total digestion. In addition, the 0.1M $NaNO_3$ method combined with total digestion is recommended for improving the reliability of BCF values.

• Journal of Life Science
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• v.31 no.4
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• pp.442-451
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• 2021

Microplastics are fragments of any type of plastic with a size less than 5 mm. Ocean pollution by microplastics is now a worldwide concern in relation to marine ecosystems and human health. The widespread contamination by microplastics means that they can be ingested by and accumulated in diverse species of wildlife, such as fish, mussels, oysters, clams, and scallops. Once ingested, the microplastics can be observed in the intestines, liver, and kidney, and even in the brain. Seafood is one of the major sources of protein intake in humans; therefore, seafood consumption could be pathway for human microplastics exposure. Accumulating evidence indicates that repeated oral exposure to microplastics induces pathologic and functional changes in the reproductive, cardiac, gastrointestinal, endocrine, and even nervous systems of rodents. Maternal exposure to microplastics during gestation and lactation alters metabolic homeostasis in the offspring. Given that seafood provides more than 20% of the total protein intake by over 310 million people worldwide, a reasonable assumption is that microplastics could be substantially accumulated in the human body and impair physiological function. In this review, we have summarized the current status of microplastics contamination in the ocean, their accumulation and toxicities in marine animals and rodents, their exposure to humans, and their potential impacts on human health.

• Biomolecules & Therapeutics
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• v.23 no.5
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• pp.428-433
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• 2015

Acetylshikonin, a natural naphthoquinone derivative compound, has been used for treatment of inflammation and cancer. In the present study, we have investigated whether acetylshikonin could regulate the NF-${\kappa}B$ signaling pathway, thereby leading to suppression of tumorigenesis. We observed that acetylshikonin significantly reduced proliferation of several cancer cell lines, including human pancreatic PANC-1 cancer cells. In addition, acetylshikonin inhibited phorbol 12-myristate 13-acetate (PMA) or tumor necrosis-${\alpha}$ (TNF-${\alpha}$)-induced NF-${\kappa}B$ reporter activity. Proteome cytokine array and real-time RT-PCR results illustrated that acetylshikonin inhibition of PMA-induced production of cytokines was mediated at the transcriptional level and it was associated with suppression of NF-${\kappa}B$ activity and matrix metalloprotenases. Finally, we observed that an exposure of acetylshikonin significantly inhibited the anchorage-independent growth of PANC-1 cells. Together, our results indicate that acetylshikonin could serve as a promising therapeutic agent for future treatment of pancreatic cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.9
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• pp.3981-3986
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• 2014

Ganoderma lucidum polysaccharides (GLP) extracted from Ganoderma lucidum have been shown to induce cell death in some kinds of cancer cells. This study investigated the cytotoxic and apoptotic effect of GLP on HCT-116 human colon cancer cells and the molecular mechanisms involved. Cell proliferation, cell migration, lactate dehydrogenase (LDH) levels and intracellular free calcium levels ($[Ca^{2+}]i$) were determined by MTT, wound-healing, LDH release and fluorescence assays, respectively. Cell apoptosis was observed by scanning and transmission electron microscopy. For the mechanism studies, caspase-8 activation, and Fas and caspase-3 expression were evaluated. Treatment of HCT-116 cells with various concentrations of GLP (0.625-5 mg/mL) resulted in a significant decrease in cell viability (P< 0.01). This study showed that the antitumor activity of GLP was related to cell migration inhibition, cell morphology changes, intracellular $Ca^{2+}$ elevation and LDH release. Also, increase in the levels of caspase-8 activity was involved in GLP-induced apoptosis. Western blotting indicated that Fas and caspase-3 protein expression was up-regulated after exposure to GLP. This investigation demonstrated for the first time that GLP shows prominent anticancer activities against the HCT-116 human colon cancer cell line through triggering intracellular calcium release and the death receptor pathway.

• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.4
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• pp.888-894
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• 2009

It has been reported that silibinin, a natural polyphenolic flavonoid, induces cell death in various cancer cell types. However, the underlying mechanisms by which silibinin induces apoptosis in human glioma cells are poorly understood. The present study was therefore undertaken to examine the effect of silibinin on glioma cell apoptosis and to determine its underlying mechanism in human glioma cells. Apoptosis was estimated by FACS analysis. Reactive oxygen species (ROS) generation and mitochondrial membrane potential (${\Psi}m$) were measured using fluorescence dyes DCFH-DA and $DiOC_6$(3), respectively. Cytochrome c release from mitochondria and caspase-3 activation were estimated by Western blot analysis using specific antibodies. Exposure of cells to 30 mM silibinin induced apoptosis starting at 6 h, with increasing effects after 12-48h in a time-dependent manner. Silibinin caused ROS generation and disruption of ym, which were associated with the silibinin-induced apoptosis. The silibinin-induced ROS generation and disruption in ym were prevented by inhibitors of mitochondrial electron transport chain. The hydrogen peroxide scavenger catalase blocked ROS generation and apoptosis induced by silibinin. Silibinin induced cytochrome c release into cytosolic fraction and its effect was prevented by catalase and cyclosporine A. Silibinin treatment caused caspase-3 activation, which was inhibited by DVED-CHO and cyclosporine A. Pretreatment of caspase inhibitors also protected against the silibinin-induced apoptosis. These findings indicate that ROS generation plays a critical role in the initiation of the silibinin-induced apoptotic cascade by mediation of the mitochondrial apoptotic pathway including the disruption of ${\Psi}m$, cytochrome c release, and caspase-3 activation.

• Biomolecules & Therapeutics
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• v.28 no.5
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• pp.465-472
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• 2020

Colorectal cancer (CRC) is one of the most malignant type of cancers and its incidence is steadily increasing, due to life style factors that include western diet. Abnormal activation of canonical Wnt/β-catenin signaling pathway plays an important role in colorectal carcinogenesis. Therefore, targeting Wnt/β-catenin signaling has been considered a crucial strategy in the discovery of small molecules for CRC. In the present study, we found that Nodosin, an ent-kaurene diterpenoid isolated from Isodon serra, effectively inhibits the proliferation of human colon cancer HCT116 cells. Mechanistically, Nodosin effectively inhibited the overactivated transcriptional activity of β-catenin/T-cell factor (TCF) determined by Wnt/β-catenin reporter gene assay in HEK293 and HCT116 cells. The expression of Wnt/β-catenin target genes such as Axin2, cyclin D1, and survivin were also suppressed by Nodosin in HCT116 cells. Further study revealed that a longer exposure of Nodosin induced the G₂/M phase cell cycle arrest and subsequently apoptosis in HCT116 cells. These findings suggest that the anti-proliferative activity of Nodosin in colorectal cancer cells might in part be associated with the regulation of Wnt/β-catenin signaling pathway.

• International Journal of Stem Cells
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• v.16 no.3
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• pp.315-325
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• 2023

Background and Objectives: Glioblastoma (GBM) is an aggressive primary brain tumor characterized by its heterogeneity and high recurrence and lethality rates. Glioblastoma stem cells (GSCs) play a crucial role in therapy resistance and tumor recurrence. Therefore, targeting GSCs is a key objective in developing effective treatments for GBM. The role of Parathyroid hormone-related peptide (PTHrP) in GBM and its impact on GSCs remains unclear. This study aimed to investigate the effect of PTHrP on GSCs and its potential as a therapeutic target for GBM. Methods and Results: Using the Cancer Genome Atlas (TCGA) database, we found higher expression of PTHrP in GBM, which correlated inversely with survival. GSCs were established from three human GBM samples obtained after surgical resection. Exposure to recombinant human PTHrP protein (rPTHrP) at different concentrations significantly enhanced GSCs viability. Knockdown of PTHrP using target-specific siRNA (siPTHrP) inhibited tumorsphere formation and reduced the number of BrdU-positive cells. In an orthotopic xenograft mouse model, suppression of PTHrP expression led to significant inhibition of tumor growth. The addition of rPTHrP in the growth medium counteracted the antiproliferative effect of siPTHrP. Further investigation revealed that PTHrP increased cAMP concentration and activated the PKA signaling pathway. Treatment with forskolin, an adenylyl cyclase activator, nullified the antiproliferative effect of siPTHrP. Conclusions: Our findings demonstrate that PTHrP promotes the proliferation of patient-derived GSCs by activating the cAMP/PKA signaling pathway. These results uncover a novel role for PTHrP and suggest its potential as a therapeutic target for GBM treatment.