• Biomolecules & Therapeutics
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• v.11 no.2
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• pp.112-118
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• 2003

1-Methylated $\beta$-carbolines (harmaline and harmalol) and antioxidants (N-acetylcysteine and ascorbate) reduced the loss of cell viability in differentiated PC 12 cells treated with 5 mM glutamate. $\beta$-Carbolines prevented the glutamate-induced decrease in mitochondrial membrane potential, cytochrome c release and caspase-3 activation in PC 12 cells. $\beta$-Carbolines reduced the formation of reactive oxygen species and depletion of glutathione due to glutamate in PC12 cells. $\beta$-Carbolines revealed a scavenging action on hydrogen peroxide and reduced the iron and EDTA-mediated degradation of 2-deoxy-D-ribose. The results suggest that I-methylated $\beta$-carbolines attenuate the cytotoxic effect of glutamate on PC12 cells by reducing the alteration of mitochondrial membrane permeability that seems to be mediated by oxidative stress.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.11
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• pp.4893-4898
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• 2016

Objective: To investigate the impact of a Croton tiglium extract on cellular proliferation and apoptosis in a non-small cell lung cancer cell line (A549) in vitro. Methods: A Croton tiglium seed methanol extract was prepare and assessed for effects on A549 cells regarding cellular proliferation, apoptotic rates, and expression of apoptosis related genes and proteins using real-time PCR and immunofluorescence. Results: The tested Croton tiglium extract inhibited A549 cell proliferation in a dose- and time-dependent manner, with significant elevation of apoptotic indexes at various concentrations after 24 h. In addition, rates in both early and late stages were higher in treated than untreated groups, the $100{\mu}g/ml$ dose causing the highest levels of apoptosis. RT-PCR showed that A549 cells treated with $100{\mu}g/ml$ Croton tiglium extract for 24 h has markedly higher Bax mRNA expression levels and obviously lower Bcl-2 expression levels than controls, equivalent results being observed for proteins by immunofluorescence. However, the mRNA expression levels of Fas and caspase-8 were not significantly altered. Conclusion: A Croton tiglium extract can inhibit proliferation of A549 cells and promote apoptosis though Bax/Bcl-2 pathways.

• Journal of Environmental Science International
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• v.28 no.11
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• pp.993-1004
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• 2019

Chrysanthemum boreale Makino (C. boreale) is widely distributed in Asian countries, and has traditionally been used to treat various inflammatory diseases including bronchitis. In this study, we aimed to isolate biologically active compounds from leaves and stems of C. boreale. Chemical components were purified by column chromatograpy and recyclic HPLC, and characterized from their spectral data (IR, MS, NMR). Biological activity experiments were conducted for Farnesyl-protein transferase (FPTase) activity, apoptosis and nitirc oxide (NO) release. As a results, three sesquiterpene lactones were isolated. Compound 1 (4-methoxy-8-O-acetyl-10-hydroxy-2,11(13)-guaiadiene-12,6-olide) showed strong cytotoxic activities having an average growth inhibition of 50% ($GI_{50}$) value of $1.89{\mu}g/m{\ell}$ against human colon adenocarcinoma cells. Compound 1 also showed a low half maximal inhibitory concentration ($IC_{50}$) value of $10{\mu}g/m{\ell}$ for NO release. In the caspase 3 activity, compound 1 and compound 2 (8-O-(2-carbonyl-2-butyl)-3,10-dihydroxy-4,11(13) -guaiadiene-12,6-olide) exhibited 94% and 90% apoptosis inhibition activity, respectively. Compound 3 (4,8-O-diacetyl -10-hydroxy-2(3),11(13)-guaiadiene-12,6-olide) showed a strong inhibitory effect on FPTase activity with 90% inhibitory activity at a concentration of $100{\mu}g/m{\ell}$. These results clearly show the presence of lactone compounds in the leaves and stems, which may partially contribute to the pharmacological activity of C. boreale.

• Journal of Life Science
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• v.25 no.11
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• pp.1331-1337
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• 2015

S-allylcysteine (SAC) is an aged garlic derived water soluble organosulfur compound and has been suggested to have anticarcinogenic activity against diverse types of cancer cells. This review summarizes the cellular signaling pathways and molecular mechanisms whereby SAC exerts its effects on cellular proliferation, apoptosis, cell cycle progression and metastasis based on the results from both in vitro and in vivo studies. SAC activates proapoptotic proteins including Bax and caspase-3, but suppresses antiapoptotic Bcl-2 family proteins to bring about cancer cell death through mitochondria-mediated intrinsic pathway. SAC also inhibits cellular proliferation by inducing cell cycle arrest in which SAC reduces expression and activation of NF-κB, cyclins, Cdks, PCNA and c-Jun, but elevates expression of cell cycle inhibitor proteins p16 and p21 through suppression of both PI3K/Akt/mTOR and MAPK/ERK signaling pathways. And, SAC inhibits invasion and metastasis of cancer cells by inducing suppression of both angiogenesis and epithelial-mesenchymal transition (EMT) through decreased cyclooxygenase (COX)-2 expression and increased E-cadherin expression which were then caused by suppression of inhibitory transcription factors Id-1 and SLUG from SAC-mediated inactivation of both MAPK/ERK and PI3K/Akt/mTOR/NF-κB signaling pathways. Furthermore, SAC prevents toxic compound-induced carcinogenesis by inducing antioxidant enzymes such as glutathione-s-transferase (GST). Thus, SAC can be considered as a potential chemotherapeutic agent for the prevention and treatment of cancer.

• Nutrition Research and Practice
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• v.11 no.2
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• pp.105-113
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• 2017

BACKGROUND/OBJECTIVES: A high-fat diet (HFD) induces obesity, which is a major risk factor for cardiovascular disease and cancer, while a calorie-restricted diet can extend life span by reducing the risk of these diseases. It is known that health effects of diet are partially conveyed through epigenetic mechanism including DNA methylation. In this study, we investigated the genome-wide hepatic DNA methylation to identify the epigenetic effects of HFD-induced obesity. MATERIALS AND METHODS: Seven-week-old male C57BL/6 mice were fed control diet (CD), calorie-restricted control diet (CRCD), or HFD for 16 weeks (after one week of acclimation to the control diet). Food intake, body weight, and liver weight were measured. Hepatic triacylglycerol and cholesterol levels were determined using enzymatic colorimetric methods. Changes in genome-wide DNA methylation were determined by a DNA methylation microarray method combined with methylated DNA immunoprecipitation. The level of transcription of individual genes was measured by real-time PCR. RESULTS: The DNA methylation statuses of genes in biological networks related to lipid metabolism and hepatic steatosis were influenced by HFD-induced obesity. In HFD group, a proinflammatory Casp1 (Caspase 1) gene had hypomethylated CpG sites at the 1.5-kb upstream region of its transcription start site (TSS), and its mRNA level was higher compared with that in CD group. Additionally, an energy metabolism-associated gene Ndufb9 (NADH dehydrogenase 1 beta subcomplex 9) in HFD group had hypermethylated CpG sites at the 2.6-kb downstream region of its TSS, and its mRNA level was lower compared with that in CRCD group. CONCLUSIONS: HFD alters DNA methylation profiles in genes associated with liver lipid metabolism and hepatic steatosis. The methylation statuses of Casp1 and Ndufb9 were particularly influenced by the HFD. The expression of these genes in HFD differed significantly compared with CD and CRCD, respectively, suggesting that the expressions of Casp1 and Ndufb9 in liver were regulated by their methylation statuses.

• Journal of Life Science
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• v.22 no.11
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• pp.1571-1586
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• 2012

On earth, there are about 5,400 kinds of mammals, of which about 1,000 kinds are herbivores. Among herbivores, about 250 kinds are known to be ruminants. As for cattle and sheep, which are ruminants, fermentation takes places mainly in their rumen; in contrast, for pigs and men, which are non-ruminants, fermentation takes place mainly in their caecum, colon, and rectum. As for the kind and dominance of rumen microorganisms, Bacteroidetes account for 51% and Firmicutes for 43%. As for the dominance of the large intestine microorganisms in men, Firmicutes account for 65% and Bacteroidetes for 25%. Cell wall components are decomposed by microorganisms, and short chain fatty acids (SCFAs) are generated through fermentation; the ratio of acetate, propionate, and butyrate generate is 60:25:15. Butyrate absorbed through the primary butyrate transporter MCT1 (mono carboxylate transports-1) in the intestines activates such SCFA receptors as GPR43 and GPR41. Butyrate has a strong anti-tumorigenic function. Butyrate is characterized by the fact that it has an effect on many cancer cells, contributes to the coordination of functions in the cells, and induces cancer apoptosis. Butyrate activates caspase but inhibits the activity of HDAC (histone deacetylase), so as to induce apoptosis. In addition, it increases p53 expression, so as to induce cell cycle arrest and apoptosis. Anti-inflammation actions of SCFA include the reduction of IL-8 expression in intestinal epithelial cells, the inhibition of NO synthesis, and the restraint of the activity of NF-${\kappa}B$ (nuclear factor ${\kappa}B$), so as to suppress the occurrence of cancers caused by inflammation. Butyrate plays an important role in maintaining physiological functions of intestinal mucous membranes and is used as a cure for inflammatory bowel disease (IBD).

• Journal of Oral Medicine and Pain
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• v.36 no.1
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• pp.11-20
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• 2011

Valproic acid (VPA) is a well-known anticonvulsive agent and has been used in the treatment of epilepsy for almost 30 years. VPA emerged in 1997 as an antineoplastic agent. And it is known that antitmor activity of VPA is associated with its targeted at histone deacetylases. 17AAG, Inhibition of HSP90 leads to the proteasome degradation of the HSP90 client proteins, such as Akt, Raf/Ras, Erk, VEGF, cyclin D and p53, and causes potent antitumor activity. It is reported that 17AAG-induced HSP90 inhibition results in prevention of cell proliferation and induction of apoptosis in several types of cancer. This study was undertaken to investigate the synergistic apoptotic effect of co-treatment with the histone deacetylases inhibitor, VPA and the HSP90 inhibitor, 17AAG on human osteosarcoma (HOS) cells. Cell viability was evaluated by trypan-blue exclusion. Induction and augmentation of apoptosis were confirmed by Hoechst staining, flow cytometry (DNA hypoploidy and MMP change), Westen blot analysis and immunofluorescent staining. In this study, HOS cells co-treated with VPA and 17AAG showed several lines of apoptotic manifestation such as nuclear condensations, the reduction of MMP, the decrease of DNA content, the release of cytochrome c into cytosol, the translocation of AIF onto nuclei, and activation of caspase-3, caspase-7 and PARP whereas each single treated HOS cells did not. Although the single treatment of 1 mM VPA or 0.5 ${\mu}M$ 17AAG for 48 h did not induce apoptosis, the co-treatment with them induced prominently apoptosis. Therefore our data in this study provide the possibility that combination therapy with VPA and 17AAG could be considered as a novel therapeutic strategy for human osteosarcoma.

• Journal of Life Science
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• v.23 no.11
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• pp.1351-1359
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• 2013

The anti-proliferative activity of ${\beta}$-ionone was investigated on human non-small lung cancer A-549 cells (designated A-549 cells). A-549 cells were treated with various concentrations of ${\beta}$-ionone (1, 5, 10, and 15 ${\mu}M$) for two, four, and six days. Biochemical markers related to the growth inhibition of A-549 cells by ${\beta}$-ionone were measured at the second day of incubation. ${\beta}$-Ionone inhibited the growth of A-549 cells by dose-and time-dependent manners, resulting in an $IC_{50}$ of 5.0 ${\mu}g/ml$ at the second day of incubation. ${\beta}$-Ionone induced apoptosis by a dose-dependent manner. ${\beta}$-Ionone increased levels of p53, p21, and Bax proteins, but suppressed expression of the Bcl-2 protein. Similarly, ${\beta}$-ionone enhanced cytochrome c release from the mitochondria to the cytosol, and induced activation of caspase-9 and -3. Additionally, ${\beta}$-ion-one reduced $cPLA_2$ and COX-2 protein levels. These results suggest that the ${\beta}$-ionone inhibits the proliferation of A-549 cells through reciprocal regulation of Bax and Bcl-2 gene expression and suppression of $cPLA_2$ and COX-2 protein expressions.

• The Journal of Dong Guk Oriental Medicine
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• v.11
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• pp.52-57
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• 2008

Objectives. In this study, we investigate that methanol extract of Euphorbiae lathyridis Semen contributes to growth inhibitory effect on the HT-29 human colon cancer cells. Methods. Euphorbiae lathyridis Semen (ELS) was extracted with 80% methanol. HT-29 cells were treated with different concentrations of ELS extract for 24-72 hrs. Growth inhibitory effect was determined by MTT assay. Cell apoptosis was determined by surveying caspases cascades activation using Western blot. Cell cycle arrest was analyzed by flow cytometry with PI staining. Results. Exposure to ELS extract showed in inhibitory effects on HT-29 cell growth as a dose-dependent manner. Cell growth inhibition by ELS extract was related with induction of cell apoptosis with DNA fragmentation through the activation of caspases-3, caspase-9 and PARP cleavage. Conclusion. ELS extract significantly inhibited cell growth and induced cell apoptosis in HT-29 human colon cancer cells, therefore, These results suggest that ELS extract can be used as chemoprevention agent of colon cancers.

• Journal of Microbiology and Biotechnology
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• v.28 no.11
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• pp.1771-1781
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• 2018

The emergence of multidrug-resistant microorganisms, as well as fungal infectious diseases that further threaten health, especially in immunodeficient populations, is a major global problem. The development of new antifungal agents in clinical trials is inferior to the incidence of drug resistance, and the available antifungal agents are restricted. Their mechanisms aim at certain characteristics of the fungus in order to avoid biological similarities with the host. Synthesis of the cell wall and ergosterol are mainly targeted in clinical use. The need for new approaches to antifungal therapeutic agents or development alternatives has increased. This review explores new perspectives on mechanisms to effectively combat fungal infections and effective antifungal activity. The clinical drug have a common feature that ultimately causes caspase-dependent cell death. The drugs-induced cell death pathway is associated with mitochondrial dysfunction, including mitochondrial membrane depolarization and cytochrome c release. This mechanism of action also reveals antimicrobial peptides, the primary effector molecules of innate systems, to highlight new alternatives. Furthermore, drug combination therapy is suggested as another strategy to combat fungal infection. The proposal for a new approach to antifungal agents is not only important from a basic scientific point of view, but will also assist in the selection of molecules for combination therapy.