• Asian Pacific Journal of Cancer Prevention
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• v.15 no.12
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• pp.4809-4813
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• 2014

Endocrine-disrupting chemicals (EDCs) have been reported to interfere with estrogen signaling. Exposure to these chemicals decreases the immune response and causes a wide range of diseases in animals and humans. Recently, many studies showed that licorice (Glycyrrhiza glabra) root extract (LRE) commonly called "gamcho" in Korea exhibits antioxidative, chemoprotective, and detoxifying properties. This study aimed to investigate the mechanism of action of LRE and to determine if and how LRE can alleviate the toxicity of EDCs. LRE was prepared by vacuum evaporation and freeze-drying after homogenization of licorice root powder that was soaked in 80% ethanol for 72 h. We used 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as a representative EDC, which is known to induce tumors or cancers; MCF-7 breast cancer cells, used as a tumor model, were treated with TCDD and various concentrations of LRE (0, 50, 100, 200, $400{\mu}g/mL$) for 24, 48, and 72 h. As a result, TCDD stimulated MCF-7 cell proliferation, but LRE significantly inhibited TCDD-induced MCF-7 cell proliferation in a dose- and time-dependent manner. The expression of TCDD toxicity-related genes, i.e., aryl hydrocarbon receptor (AhR), AhR nuclear translocator, and cytochrome P450 1A1, was also down-regulated by LRE in a dose-dependent manner. Analysis of cell cycle distribution after treatment of MCF-7 cells with TCDD showed that LRE inhibited the proliferation of MCF-7 cells via G2/M phase arrest. Reverse transcription-polymerase chain reaction and Western blot analysis also revealed that LRE dose-dependently increased the expression of the tumor suppressor genes p53 and p27 and down-regulated the expression of cell cycle-related genes. These data suggest that LRE can mitigate the tumorigenic effects of TCDD in breast cancer cells by suppression of AhR expression and cell cycle arrest. Thus, LRE can be used as a potential toxicity-alleviating agent against EDC-mediated diseases.

• Journal of Genetic Medicine
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• v.6 no.1
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• pp.1-7
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• 2009

Epigenetic changes represented by promoter CpG island hypermethylation and histone modification are an important carcinogenetic mechanism, which is found in virtually all histologic types of human cancer. About 60-70% of human genes harbor CpG islands in their promoters and 5' exonal sequences, and some of them undergo aberrant promoter CpG island hypermethylation and subsequent downregulation of gene expression. The loss of expression in tumor suppressor or tumor-related genes results in acceleration of tumorigenic processes. In addition to regional CpG island hypermethylation, diffuse genomic hypomethylation represents an important aspect of DNA methylation changes occurring in human cancer cells and contributes to chromosomal instability. These apparently contrasting methylation changes occur not only in human cancer cells, but also in premalignant cells. CpG island hypermethylation has gained attention for not only the tumorigenic mechanistic process, but also its potential utilization as a tumor biomarker. DNA methylation markers are actively investigated for their potential uses as tumor biomarkers for diagnosis of tumors in body fluids, prognostication of cancer patients, or prediction of chemotherapeutic drug response. In this review, these aspects will be discussed in detail.

• Journal of Food Hygiene and Safety
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• v.26 no.4
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• pp.398-402
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• 2011

Cruciferous vegetables including diindolylmethane (DIM) have been shown to have anticancer activity. Especially, DIM-pPhBr and DIM-pPhF used in this study was reported to have more effective and less toxic effects than DIM. However, there is no report presenting their anti-tumorigenic activity in oral cancer. In the present study, we examined the effects of DIM-pPhBr and DIM-pPhF on the cell proliferation and apoptosis in KB human oral cancer cells. DIM-pPhBr and DIM-pPhF decreased cell proliferation and induced apoptosis evidenced by western blot analysis, DAPI staining and sub-$G_1$ population. This provides the first evidence that DIM-pPhBr and DIM-pPhF originating from Cruciferous vegetables induce apoptotic cell death in human oral cancer cells to inhibit cancer cell proliferation.

• 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).

• Food Science and Preservation
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• v.13 no.5
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• pp.649-654
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• 2006

To enhance beneficial effects of citron fruits, anticancer and antioxidant activities of citron fruits extracts were assessed with or without ascorbic acid. Total phenolic acids and flavonoids of fruits peels and flesh extracts were determined. Fruits peels contained more phenolic acids and flavonoids than those detected in flesh extracts. Scavenging activities of 1,1-diphenyl-2-picrylhydrazyl radicals and reducing powers were increased depending on the concentration. The antioxidant activities on oxidation of linoleic acid emulsion incubated at $50^{\circ}C$ were increased but the effect was small to that of butylated hydroxy toluene and ascorbic acid. The anti-tumorigenic effect of these compounds were investigated. They were shown to inhibit the in vitro proliferation of four human tumorigenic cell lines, HT-29, MCF-7, DU-145 and HepG2, in a doso-dependent manner. This study demonstrated that the antioxidant and anticancer activities of citron fruits extracts were derived from their phenols and flavonoids.

• Korean Journal of Radiology
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• v.19 no.6
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• pp.1099-1109
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• 2018

Objective: In a proof of concept study, we compared no-touch radiofrequency ablation (NtRFA) in bipolar mode with conventional direct tumor puncture (DTP) in terms of local tumor control (LTC), peritoneal seeding, and tumorigenic factors, in the rabbit VX2 subcapsular hepatic tumor model. Materials and Methods: Sixty-two rabbits with VX2 subcapsular hepatic tumors were divided into three groups according to the procedure: DTP-RFA (n = 25); NtRFA (n = 25); and control (n = 12). Each of the three groups was subdivided into two sets for pathologic analysis (n = 24) or computed tomography (CT) follow-up for 6 weeks after RFA (n = 38). Ultrasonography-guided DTP-RFA and NtRFA were performed nine days after tumor implantation. LTC was defined by either achievement of complete tumor necrosis on histopathology or absence of local tumor progression on follow-up CT and autopsy. Development of peritoneal seeding was also compared among the groups. Serum hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) were measured via ELISA (Elabscience Biotechnology Co.) after RFA for tumorigenic factor evaluation. Results: Regarding LTC, there was a trend in NtRFA (80%, 20/25) toward better ablation than in DTP-RFA (56%, 14/25) (p = 0.069). Complete tumor necrosis was achieved in 54.5% of DTP-RFA (6/11) and 90.9% of NtRFA (10/11). Peritoneal seeding was significantly more common in DTP-RFA (71.4%, 10/14) than in NtRFA (21.4%, 3/14) (p = 0.021) or control (0%). Elevations of HGF, VEGF or IL-6 were not detected in any group. Conclusion: No-touch radiofrequency ablation led to lower rates of peritoneal seeding and showed a tendency toward better LTC than DTP-RFA.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.4
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• pp.2571-2575
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• 2013

AKT1 is a member of the serine/threoine AGC protein kinase family involved in thyroid cancer metabolism, growth, proliferation and survival. It is overexpressed in thyroid tumors. In this study, we designed two AKT1 specific DNAzymes (DRz1 and DRz2) that target AKT1 mRNA. The results showed that DRz1 could decrease the expression of AKT1 by 58%. Furthermore, DRz1 significantly inhibited cell proliferation, induced apoptosis and inhibited invasion in SW597 cells. In addition, down-regulation of survivin expression was associated with decreased caspase-3, VEGF and MMP2 in SW597 cells after 24 h. In our study, the efficacy of DRz1 in decreasing AKT1 protein levels were better than DRz2. AKT1-DRz1 might have anti-tumorigenic activity and may provide the basis for a novel therapeutic intervention in thyroid cancer treatment.

• BMB Reports
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• v.50 no.12
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• pp.599-600
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• 2017

Many studies have focused on the tumor suppressive role of $TGF-{\beta}$ signaling during the early stages of tumorigenesis by activating the target genes involved in cytostasis and apoptosis. We investigated the effects of $TGF-{\beta}$ inhibition on early tumorigenesis in the liver, by employing diverse inhibitory methods. Strikingly, $TGF-{\beta}$ inhibition consistently suppressed hepatic tumorigenesis that was induced either by activated RAS plus p53 downregulation or by the co-activation of RAS and TAZ signaling; this demonstrates the requirements for canonical $TGF-{\beta}$ signaling in tumorigenesis. Moreover, we found that Snail is the target gene of the $TGF-{\beta}$ signaling pathway that promotes hepatic carcinogenesis. The knockdown of Snail suppressed the early tumorigenesis in the liver, as did the $TGF-{\beta}$ inhibition, while the ectopic expression of Snail restored tumorigenesis that was suppressed by the $TGF-{\beta}$ inhibition. Our findings establish the oncogenic $TGF-{\beta}$-Smad-Snail signaling axis during the early tumorigenesis in the liver.

• BMB Reports
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• v.49 no.12
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• pp.651-652
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• 2016

EphA2 has been implicated in amplifying ErbB2 tumorigenic signaling. One protein that interacts with EphA2 is the Anks1a PTB adaptor. However, the precise role of Anks1a in EphA2-mediated tumorigenesis is unclear. We demonstrated that Anks1a localizes to the ER upon phosphorylation and that the Ankyrin repeats and PTB of Anks1a bind to EphA2 and Sec23, respectively. Thus, Anks1a facilitates the selective packaging of EphA2 into COPII vesicles. Additionally, Anks1a knockout mice, a phenocopy of EphA2 knockout mice, exhibited markedly reduced ErbB2-induced breast tumorigenesis. Strikingly, ErbB2 did not localize to the cell surface following Anks1a knockdown in primary mammary tumor cells over-expressing ErbB2. Importantly, EphA2 was critical for stabilizing ErbB2 through complex formation, but its interaction with Anks1a also facilitated ErbB2 loading into COPII carriers. These findings suggest a novel role for Anks1a in the molecular pathogenesis of breast tumors and possibly other human diseases.

• BMB Reports
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• v.48 no.3
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• pp.159-165
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• 2015

Although the short isoform of ErbB3-binding protein 1 (Ebp1), p42 has been considered to be a potent tumor suppressor in a number of human cancers, whether p42 suppresses tumorigenesis of lung cancer cells has never been clarified. In the current study we investigated the tumor suppressor role of p42 in non-small cell lung cancer cells. Our data suggest that the expression level of p42 is inversely correlated with the cancerous properties of NSCLC cells and that ectopic expression of p42 is sufficient to inhibit cell proliferation, anchorage-independent growth, and invasion as well as tumor growth in vivo. Interestingly, p42 suppresses Akt activation and overexpression of a constitutively active form of Akt restores the tumorigenic activity of A549 cells that is ablated by exogenous p42 expression. Thus, we propose that p42 Ebp1 functions as a potent tumor suppressor of NSCLC through interruption of Akt signaling.