• Asian Pacific Journal of Cancer Prevention
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• v.15 no.23
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• pp.10407-10412
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• 2015

Background: ${\beta}$-elemene, extracted from herb medicine Curcuma wenyujin has potent anti-tumor effects in various cancer cell lines. However, the activity of ${\beta}$-elemene against glioma cells remains unclear. In the present study, we assessed effects of ${\beta}$-elemene on human glioma cells and explored the underlying mechanism. Materials and Methods: Human glioma U87 cells were used. Cell proliferation was determined with MTT assay and colony formation assay to detect the effect of ${\beta}$-elemene at different doses and times. Fluorescence microscopy was used to observe cell apoptosis with Hoechst 33258 staining and change of glioma apoptosis and cell cycling were analyzed by flow cytometry. Real-time quantitative PCR and Western-blotting assay were performed to investigated the influence of ${\beta}$-elemene on expression levels of Fas/FasL, caspase-3, Bcl-2 and Bax. The experiment was divided into two groups: the blank control group and ${\beta}$-elemne treatment group. Results: With increase in the concentration of ${\beta}$-elemene, cytotoxic effects were enhanced in the glioma cell line and the concentration of inhibited cell viability ($IC_{50}$) was $48.5{\mu}g/mL$ for 24h. ${\beta}$-elemene could induce cell cycle arrest in the G0/G1 phase. With Hoechst 33258 staining, apoptotic nuclear morphological changes were observed. Activation of caspase-3,-8 and -9 was increased and the pro-apoptotic factors Fas/FasL and Bax were upregulated, while the anti-apoptotic Bcl-2 was downregulated after treatment with ${\beta}$-elemene at both mRNA and protein levels. Furthermore, proliferation and colony formation by U87 cells were inhibited by ${\beta}$-elemene in a time and does-dependent manner. Conclusions: Our results indicate that ${\beta}$-elemene inhibits growth and induces apoptosis of human glioma cells in vitro. The induction of apoptosis appears to be related with the upregulation of Fas/FasL and Bax, activation of caspase-3,-8 and -9 and downregulation of Bcl-2, which then trigger major apoptotic cascades.

• The Journal of Korean Medicine
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• v.26 no.2 s.62
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• pp.77-84
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• 2005

Objectives: Chunghyul-dan is a combinatorial herbal medicine, and previous studies reported it had therapeutic effects for microangiopathy, which is a major part. in the progression of stroke, as well as having anti-hypertensive, anti-hyperlipidemic, anti-apoptotic, anti-oxidative, and anti-inflammatory activities, Therefore, we examined the inhibitory effect of Chunghyul-dan on stroke occurrence in patients with silent brain infarction. Methods: We prescribed Chunghyul-dan at 600 mg a day to patients with silent brain infarction confirmed by brain MRI, and monitored stroke occurrence, drug compliances, and adverse effects for 1 year, We then performed follow-up brain MRI to detect new vascular lesions after 1 year of Chunghyul-dan medication. As for the subjects lost to follow-up, we assessed their prognosis after 1 year by telephone. Results: There were twenty-one subjects who were treated with Chunghyul-dan for more than 1 year, None of them experienced new clinical syndromes characterized by rapidly developing clinical symptoms and signs of focal and at times global loss of brain function, which could be accompanied with evidence of stroke occurrence, or any adverse effects during the Chunghyul-dan medication period. These results might be explained by various biochemical effects of Chunghyul-dan on microangiopathy, which is closely related with cell cycle progression, hypertension, hyperlipidemia, vascular inflammation, and oxidative damage. Of the 10 subjects lost to follow-up, six were reached; two of them had stroke occurrence. Conclusions: We suggest Chunghyul-dan could be useful for prevention of stroke occurrence in patients with silent brain infarction by preventing the progression of microangiopathy. Further study with a randomized controlled trial is needed to confirm this suggestion.

• Journal of Life Science
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• v.14 no.1
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• pp.61-66
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• 2004

Many studies have been widely carried out to find out new compound having anti-cancer activity from animals and plants. Some plants have been reported to have anti-lancer effects. However, the anti-cancer effect of edible plants were seldomly evaluated. Therefore we investigated the anticancer effects of edible plants (10 samples) easily available around us by measuring number of survival cancer cells after treatment with direct cell counting and MTT analysis, and by examining the morphological change under the electromicroscope. Of the 10 samples tested, Equisetum arvense L., Lactuca dentata Mokino. var. faviflora Makino. showed moderate anti-cancer effects even at the concentration of 10 $\mul/ml$ against MCF-7 adenocarcinoma cell line. Of them, Capsicum annuum L. had most potent anti-cancer activity against MCF-7 adenocarcinoma cell line showing proliferation inhibited, morphological change and apoptosis at the concentration of 2 $\mul/ml$.

• Journal of Marine Bioscience and Biotechnology
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• v.13 no.2
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• pp.86-93
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• 2021

A high salt diet contributes to kidney damage by causing hypoxia and oxidative stress. Recently, an increase in dietary salt has been reported to induce an inflammatory phenotype in immune cells, further contributing to kidney damage. However, studies on the exact mechanism and role of a high salt diet on the inflammatory response in the kidneys are still insufficient. In this study, a cisplatin-induced acute kidney injury model using C57BL/6 mice was used to analyze the effect of salt intake on kidney injury. Results showed that high salt administration aggravated kidney edema in mice induced by treatment with cisplatin. Moreover, the indicators of kidney and liver function impairment were significantly increased in the group cotreated with high salt compared with that treated with cisplatin alone. Furthermore, the exacerbation of kidney damage by high salt administration was also associated with a decrease in the number of cells in the immune regulatory system. Additionally, high salt administration further decreased renal perfusion functions along with increased cisplatin-induced damage to proximal tubules. This was accompanied by increased expression of T cell immunoglobulin, mucin domain 1 (a biomarker of kidney injury), and Bax (a pro-apoptotic factor). Moreover, cisplatin-induced expression of proinflammatory mediators and cytokines, including cyclooxygenase-2 and tumor necrosis factor-α in kidney tissue, was further increased by high salt intake. Therefore, these results indicate that the kidney's inflammatory response by high salt treatment can further promote kidney damage caused by various pathological factors.

• Applied Microscopy
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• v.38 no.4
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• pp.293-306
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• 2008

The essential factor of acute respiratory distress syndrome (ARDS), an acute lung injury accompanied commonly by sepsis syndrome is accumulation of neutrophils in lung tissue. The study attempted to confirm whether a lung injury would be decreased with the anti-inflammatory effect of germanium by the treated germanium prior to the development of ARDS and whether nitric oxide influence in suppressing a lung injury. Test groups were divided in the following structure for experiment; CON that has been administered with sodium chloride to airway, LPS administered with endotoxin for 5 hours in the same amount and 5 hours of endotoxin administered Ge+LPS following 1 hours of pre-treated germanium. The result of a test using experimental animals, infilteration of neutrophils (p<0.001) in bronchoalveolar lavage fluid (BALF) was significantly decreased, the structure of lung tissue was preserved relatively well, and much neutrophils with distinct positive were observed on tunel staining which showed increase of apoptotic neutrophils in the pre-treated germanium group compare to the endotoxin administrated group. In observation of ultrastructural changes of cell in BALF, phagocytic alveolar macrophage was increased in alveolar space, the nucleus of most engulfed neutrophils were condensed, and some apoptosis neutrophils appears to be DNA fragmentation and effacement of cellular organelles were found in intercellular matrix in the pre-treated germanium group. However, the nitric oxide showed increase in all the groups excluding CON, and the nitric oxide effect such as degranulation diminishing of mast cells and apoptosis increase of neutrophils in the pre-treated group only. The situation appears that there was change in internal environment of the experimental animal by the pre-treated germanium before the nitric oxide is produced and the anti-inflammatory effect activated the pre-processed germanium by nitric oxide which activated following the change. Therefore, the nitric oxide created from macrophage in accordance with the pre-treated germanium appears to influence in alleviating a lung injury. Accordingly, acute lung injury is alleviated by the anti-inflammatory effect of germanium such as inhibition of neutrophils migration, induction of neutrophil apoptosis and increase of phagocytic function of phagocyte, and the nitric oxide produced from activated macrophage by germanium would influence in suppressing a lung injury.

• The Journal of Korean Medicine
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• v.30 no.3
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• pp.1-14
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• 2009

Objectives : Alzheimer's disease (AD) is characterized by neuronal loss and extracellular senile plaque. Moreover, the cellular actions of ${\beta}$-amyloid (A${\beta}$ play a causative role in the pathogenesis of AD. This study was designed to determine whether Woo-Gui-Um, a commonly used Korean herbal medicine, has the ability to protect cortical and hippocampal neurons against A${\beta}_{25-35}$ neurotoxicity Methods : In the present study, the authors investigated the preventative effects of the water extract of Woo-Gui-Um in a mouse model of AD. Memory impairment was induced by intraventricularly (i.c.v.) injecting A${\beta}_{25-35}$ peptides into mice. Woo-Gui-Um extract was then administered orally (p.o.) for 14 days. In addition, A${\beta}_{25-35}$ toxicity on the hippocampus was assessed immunohistochemically, by staining for Tau, MAP2, TUNEL, and Bax, and by performing an in vitro study in PC12 cells. Results : Woo-Gui-Um extract had an effect to improve learning ability and memory score in the water maze task. Woo-Gui-Um extract had significant neuroprotective effects in vivo against oxidative damage and apoptotic cell death of hippocampal neurons caused by i.c.v. A${\beta}_{25-35}$. In addition, Woo-Gui-Um extract was found to have a protective effect on A${\beta}_{25-35}$-induced apoptosis, and to promote neurite outgrowth of nerve growth factor (NGF)-differentiated PC12 cells. Conclusions : These results suggest that Woo-Gui-Um extract reduces memory impairment and Alzheimer's dementia via an anti-apoptotic effect and by regulating Tau and MAP2 in the hippocampus.

• Korean Journal of Medicinal Crop Science
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• v.14 no.2
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• pp.70-76
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• 2006

Paeoniae radix has been widely used for its anti-allergic, anti-inflammatory and analgesic effects, and demonstrated to have anticonvulsant, memory enhancing and anxiolytic activities. The present study was performed to examine the protective effect of methanol extract of Paeoniae radix (PR) from Paeoniae Japonica Miyabe et Takeda (Paeoniaceae) on hydrogen peroxide $(H_2O_2)-induced$ neurotoxicity using cultured rat cerebral cortical neuron. $H_2O_2$ produced a concentration-dependent reduction of neuronal viability, PR, over a concentration range of 10 to $100\;{\mu}g/ml$ showed concentration-dependent decrease of the $H_2O_2$$(100\;{\mu}M)-induced$ neuronal cell death, as assessed by a 3-[4,5-dimethylthiazol-2-yl]-2,5-di-phenyl-tetrazolium bromide assay and the number of apoptotic nuclei, evidenced by Hoechst 33342 staining. PR $(100\;{\mu}g/ml$ inhibited $100\;{\mu}M$ $H_2O_2-induced$ elevation of the cytosolic $Ca^{2+}$ concentration $([Ca^{2+}]_c)$, which was measured by a fluorescent dye, flue-4 AM. PR $(50\;{\mu}g/ml$ inhibited glutamate release into medium induced by $100\;{\mu}M$ $H_2O_2$, which was measured by HPLC, and generation of reactive oxygen species (ROS). These results suggest that PR may mitigate the $H_2O_2-induced$ neurotoxiciy by interfering with the increase of $[Ca^{2+}]_c$, and then inhibiting glutamate release and generation of ROS in cultured neurons.

• BMB Reports
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• v.47 no.5
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• pp.262-267
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• 2014

Bcl-2 interacting cell death suppressor (Bis) has been shown to have anti-apoptotic and anti-stress functions. Recently, increased Bis expression was reported to correlate with glioma aggressiveness. Here, we investigated the effect of Bis knockdown on the acquisition of the invasive phenotype of A172 glioma cells, induced by 12-O-Tetradecanoylphorbol-3-acetate (TPA), using a Transwell assay. Bis knockdown resulted in a significant decrease in the migration and invasion of A172 cells. Furthermore, Bis knockdown notably decreased TPA-induced matrix metalloproteinase-9 (MMP-9) activity and mRNA expression, as measured by zymography and quantitative real time PCR, respectively. A luciferase reporter assay indicated that Bis suppression significantly down-regulated NF-${\kappa}B$-driven transcription. Finally, we demonstrated that the rapid phosphorylation and subsequent degradation of $I{\kappa}B-{\alpha}$ induced by TPA was remarkably delayed by Bis knockdown. These results suggest that Bis regulates the invasive ability of glioma cells elicited by TPA, by modulating NF-${\kappa}B$ activation, and subsequent induction of MMP-9 mRNA.

• International Journal of Oral Biology
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• v.43 no.2
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• pp.69-76
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• 2018

Oral squamous cell carcinoma (OSCC) is the most common type of oral malignancy. Numerous therapies have been proposed for its cure. Research is continually being conducted to develop new forms of treatment as current therapies are associated with numerous side-effects. Luteolin, a common dietary flavonoid, has been demonstrated to possess strong anti-cancer activity against various human cancer cell lines. Nevertheless, research into luteolin-based anticancer activity against oral cancer remains scarce. Thus, the objective of this study was to assess the effect of luteolin as an anti-cancer agent. After treatment with luteolin, Ca9-22 and CAL-27 oral cancer cells showed condensed nuclei and enhanced apoptotic rate with evidence of mitochondria-mediated apoptosis. Epithelialmesenchymal transition (EMT) is closely related to tumor migration and invasion. Luteolin suppressed cancer cell invasion and migration in the current study. Elevated expression of E-cadherin, an adherens junction protein, was evident in both cell lines after luteolin treatment. Luteolin also significantly inhibited transcription factors (i.e., N-cadherin, Slug, Snail, Twist, and ZEB-1) that regulated expression of tumor suppressors such as E-cadherin based on Western blot analysis and quantitative PCR. Thus, luteolin could induce mitochondrial apoptosis and inhibit cancer cell invasion and migration by suppressing EMT-induced transcription factors.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.4
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• pp.457-465
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• 2018

The expression of BCL-2 interacting cell death suppressor (BIS), an anti-stress or anti-apoptotic protein, has been shown to be regulated at the transcriptional level by heat shock factor 1 (HSF1) upon various stresses. Recently, HSF1 was also shown to bind to BIS, but the significance of these protein-protein interactions on HSF1 activity has not been fully defined. In the present study, we observed that complete depletion of BIS using a CRISPR/Cas9 system in A549 non-small cell lung cancer did not affect the induction of heat shock protein (HSP) 70 and HSP27 mRNAs under various stress conditions such as heat shock, proteotoxic stress, and oxidative stress. The lack of a functional association of BIS with HSF1 activity was also demonstrated by transient downregulation of BIS by siRNA in A549 and U87 glioblastoma cells. Endogenous BIS mRNA levels were significantly suppressed in BIS knockout (KO) A549 cells compared to BIS wild type (WT) A549 cells at the constitutive and inducible levels. The promoter activities of BIS and HSP70 as well as the degradation rate of BIS mRNA were not influenced by depletion of BIS. In addition, the expression levels of the mutant BIS construct, in which 14 bp were deleted as in BIS-KO A549 cells, were not different from those of the WT BIS construct, indicating that mRNA stability was not the mechanism for autoregulation of BIS. Our results suggested that BIS was not required for HSF1 activity, but was required for its own expression, which involved an HSF1-independent pathway.