• Journal of Gastric Cancer
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• v.2 no.4
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• pp.213-220
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• 2002

Purpose: The cDNA microarray provides a powerful alternative with an unprecedented view in monitoring geneexpression levels and leads to discoveries of regulatory pathways involved in complicated biological processes. Our aim is to explore the different gene-expression patterns in gastric adenocarcinomas. Materials and Methods: By using a cDNA microarray representing 4,600 cDNA clusters, we studied the expression profiling in 10 paired gastric adenocarcinoma samples and in adjacent noncancerous gastric tissues from the same patients. Alterations in the gene-expression levels were confirmed by Vsing Northern blots and reverse-transcription PCR (RT-PCR) in all of 4 randomly selected genes. Results: Genes those were expressed differently in cancer ous and noncancerous tissues were identified. 44 (of which 26 were known) and 92 (of which 43 were known) genes or cDNA were up- and down-regulated, respectively, in more than $80\%$ of the gastric adenocarcinoma samples. In cancer ous tissues, genes related to gene/protein expression, cellcycle regulation, and metabolism were mostly up-regulated whereas genes related to the oncogene/tumor suppressor gene, cell structure/motility, and immunology were mostly down-regulated. The semi-quantitative RT-PCR results for the four genes we tested were consistent with the array findings. Conclusions: These results provide not only a new molecular basis for understanding the biological properties of gastric adenocarcinomas but also a useful resource for future development of therapeutic targets and diagnostic markers for gastric adenocarcinomas.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.1851-1855
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• 2016

Tamoxifen is a pharmacological estrogen inhibitor that binds to the estrogen receptor (ER) in breast cells. However, it shows an estrogenic effect in other organs, which causes adverse drug reactions (ADRs). The sulfotransferase 1A1 (SULT1A1) enzyme encoded by the SULT1A1 gene is involved in estrogen metabolism. Previous research has suggested that the SULT1A1 copy number is linked with the plasma estradiol (E2) concentration. Here, a total of 34 premenopausal breast cancer patients, selected from the Thai Tamoxifen (TTAM) Project, were screened for their SULT1A1 copy number, plasma E2 concentration and ADRs. The mean age was $44.3{\pm}11.1years$, and they were subtyped as ER+/progesterone receptor (PR)+ (28 patients), ER+/PR- (5 patients) and ER-/PR- (1 patient). Three patients reported ADRs, which were irregular menstruation (2 patients) and vaginal discharge (1 patient). Most (33) patients had two SULT1A1 copies, with one patient having three copies. The median plasma E2 concentration was 1,575.6 (IQR 865.4) pg/ml. Patients with ADRs had significantly higher plasma E2 concentrations than those patients without ADRs (p = 0.014). The plasma E2 concentration was numerically higher in the patient with three SULT1A1 copies, but this lacked statistical significance.

• Biomolecules & Therapeutics
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• v.27 no.1
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• pp.48-53
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• 2019

Reactive oxygen species (ROS) are widely generated in biological processes such as normal metabolism and response to xenobiotic exposure. While ROS can be beneficial or harmful to cells and tissues, generation of ROS by diverse anti-cancer drugs or phytochemicals plays an important role in the induction of apoptosis. We recently identified a derivative of naphthalene, MS-5, that induces apoptosis of an ovarian cell, CAOV-3. Interestingly, MS-5 induced apoptosis by down-regulating the ROS. Cell viability was evaluated by water-soluble tetrazolium salt (WST-1) assay. Apoptosis was evaluated by flow cytometry analysis. Intracellular ROS ($H_2O_2$), mitochondrial superoxide, mitochondrial membrane potential (MMP) and effect on cycle were determined by flow cytometry. Protein expression was assessed by western blotting. The level of ATP was measured using ATP Colorimetric/Fluorometric Assay kit. MS-5 inhibited growth of ovarian cancer cell lines, CAOV-3, in a concentration- and time-dependent manner. MS-5 also induced G1 cell cycle arrest in CAOV-3 cells, while MS-5 decreased intracellular ROS generation. In addition, cells treated with MS-5 showed the decrease in MMP and ATP production. In this study, we found that treatment with MS-5 in CAOV-3 cells induced apoptosis but decreased ROS level. We suspect that MS-5 might interfere with the minimum requirements of ROS for survival. These perturbations appear to be concentration-dependent, suggesting that MS-5 may induce apoptosis by interfering with ROS generation. We propose that MS-5 may be a potent therapeutic agent for inducing apoptosis in ovarian cancer cell through regulation of ROS.

• Genomics & Informatics
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• v.21 no.2
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• pp.23.1-23.9
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• 2023

The mammalian sirtuin family, consisting of SIRT1-SIRT7, plays a vital role in various biological processes, including cancer, diabetes, neurodegeneration, cardiovascular disease, cellular metabolism, and cellular homeostasis maintenance. Due to their involvement in these biological processes, modulating sirtuin activity seems promising to impact immuneand aging-related diseases, as well as cancer pathways. However, more understanding is required regarding the safety and efficacy of sirtuin-targeted therapies due to the complex regulatory mechanisms that govern their activity, particularly in the context of multiple targets. In this study, the interaction landscape of the sirtuin family was analyzed using a systems biology approach. A sirtuin protein-protein interaction network was built using the Cytoscape platform and analyzed using the NetworkAnalyzer and stringApp plugins. The result revealed the sirtuin family's association with numerous proteins that play diverse roles, suggesting a complex interplay between sirtuins and other proteins. Based on network topological and functional analysis, SIRT1 was identified as the most prominent among sirtuin family members, demonstrating that 25 of its protein partners are involved in cancer, 22 in innate immune response, and 29 in aging, with some being linked to a combination of two or more pathways. This study lays the foundation for the development of novel therapies that can target sirtuins with precision and efficacy. By illustrating the various interactions among the proteins in the sirtuin family, we have revealed the multifaceted roles of SIRT1 and provided a framework for their possible roles to be precisely understood, manipulated, and translated into therapeutics in the future.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.13
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• pp.5557-5563
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• 2015

Background: Cholelithiasis is associated in 54%-98% of patients with carcinoma of the gallbladder, and a high incidence among females suggests a role of female hormones in the etiology of the disease. Cytochrome $P450C17{\alpha}$ (CYP-17) is a key enzyme involved in estrogen metabolism and polymorphisms in CYP-17 are associated with altered serum levels of estrogens. Thus, we investigated whether the CYP-17 MspA1 gene polymorphism might impact on risk of gall bladder cancers or gallstones, as well as to determine if this gene polymorphism might be linked with estrogen serum levels and lipid profile among the North Indian gall bladder cancer or gallstone patients. Materials and Methods: CYP-17 gene polymorphisms (MspA1) were genotyped with PCR-RFLP in cancer patients (n=96), stone patients (n=102), cancer + stone patients (n=52) and age/sex matched control subjects (n= 256). Lipid profile was estimated using a commercial kit and serum estrogen was measured using ELISA. Results: The majority of the patients in all groups were females. The lipid profile and estrogen level were significantly higher among the study as compared to control groups. The frequency of mutant allele A2 of CYP17 MspA1 gene polymorphism was higher among cancer (OR=5.13, 95% CI+3.10-8.51, p=0.0001), stone (OR=5.69, 95%CI=3.46-9.37, p=0.0001) and cancer + stone (OR=3.54, 95%CI=1.90-6.60, p=0.0001) when compared with the control group. However there was no significant association between genotypes of CYP17 MspA1 gene polymorphism and circulating serum level of estrogen and lipid profile. Conclusions: A higher frequency of mutant genotype A1A2 as well as mutant allele A2 of CYP-17 gene polymorphism is significantly associated with risk of gallbladder cancer and stones. Elevated levels of estrogen and an altered lipid profile can be used as predictors ofgall bladder stones and cancer in post menopausal females in India.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.14
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• pp.5621-5626
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• 2014

N-acetyltransferase 2 (NAT2) is a polymorphic enzyme that plays an important role in the metabolism of various potential carcinogens. In recent years, a number of studies have been carried out to investigate the relationship between the rs1799930 and rs1799931 polymorphism in NAT2 and cancer risk in multiple populations for different types of cancer. However, the results were not consistent. Therefore, we performed a meta-analysis to further explore the relationship between NAT2 polymorphism and the risk of cancer. A total of 21 studies involving 15, 450 subjects for rs1799930 and 13, 011 subjects for rs1799931 were included in this meta-analysis. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess strength of associations. We also evaluated the publication bias and performed a sensitivity analysis. Overall, our results showed an apparent significant association between the NAT2 rs1799930 polymorphism and cancer susceptibility in Asians (GA vs. GG: OR=1.22, 95% CI=1.03-1.45; dominant model: OR=1.22, 95% CI=1.03-1.43) and population-based controls (GA vs. GG: OR=1.10, 95% CI=1.01-1.19; dominant model: OR=1.09, 95% CI=1.01-1.18). In contrast, a significant association was observed between the NAT2 rs1799931 G>A polymorphism and decreased cancer susceptibility in overall meta-analysis (AA vs. GG: OR=0.55, 95% CI=0.33-0.93; GA vs. GG: OR=1.00, 95% CI=0.88-1.14; dominant model: OR=0.97, 95% CI=0.86-1.10; recessive model: OR=0.56, 95% CI=0.34-0.94) and the Asian group (AA vs. GG: OR=0.50, 95% CI=0.26-0.94; recessive model, OR=0.50, 95% CI=0.27-0.94). We found that the NAT2 rs1799930 may be a risk factor, while the NAT2 rs1799931 polymorphism is associated with a decreased risk of cancer and is likely a protective factor against cancer development.

• Environmental Mutagens and Carcinogens
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• v.18 no.2
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• pp.77-82
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• 1998

In order to compare the suppressive effect of galangin on the genotoxicity by N-methyl-N-nitrosourea (MNU) or benzo[a]pyrene B(a)P, in vivo micronycleus test using mouse peripheral blood and in vitro sister chromatid exchange(SCE) test using mouse spleen lymphocytes were performed. MNU or B(a)P-induced micronucleated reticulocytes in vivo was decreased by the simultaneous treatment of galangin. MNU or B(a)P-induced SCEs in vitro was also decreased by the simultaneous treatment of galangin. On the other hand, the determinations of [$^3$H]MNU-induced total DNA binding and methylated DNA were performed to find out the mechanism of action. [$^3$H]MNU-induced total DNA binding was inhibited by the treatment of galangin in calf thymus DNA. HPLC analysis of DNA hydrolysates showed that galangin caused a decrease of 7-methyl guanine and $O^{6}$-methyl guanine in calf thymus DNA. To elucidate the action mechanism of galangin against B(a)P, alteration of B(a)P metabolism was studied. Galangin inhibited B(a)P metabolism in the presence of S-9 mix and decreased B(a)P-DNA binding in calf thymus DNA with S-9 mix.

• The Journal of Korean Medicine
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• v.37 no.2
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• pp.76-84
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• 2016

Objectives: We evaluated the anti-fatigue effects of Rh2-enriched Korean ginseng (Ginseng Rh2+) using a forced exercise-induced chronic fatigue mouse model. Methods: ICR male mice were subjected to running wheel for 1 h, 5 days/week during 4 weeks, and running velocity was gradually increased. Each running session was followed by oral administration of distilled water, Ginseng Rh2+ (150 or 300 mg/kg), or N-acetyl-L-cysteine (NAC, 100 mg/kg) 1 h later. The exercise tolerance and forced swimming test were performed to evaluate the fatigue condition. Results: Chronic forced exercise reduced the physical activity, as evidenced by the behavioral tests, which were notably ameliorated by Ginseng Rh2+ treatment. Ginseng Rh2+ treatment also attenuated the alterations of energy metabolism and oxidative stress in skeletal muscle tissues and/or sera, including malondialdehyde (MDA), lactate concentration and its related factors (lactate dehydrogenase, blood urea nitrogen, and glucose levels). Conclusion: These findings strongly suggest that Ginseng Rh2+ exerts a potent anti-fatigue effect through modulation of energy metabolism and oxidative response.

• Journal of Society of Preventive Korean Medicine
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• v.18 no.3
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• pp.117-128
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• 2014

Objective : It is known that Pueriaria lobata has an anti-osteoporetic effect, anti-cancer effect, anti-pyretic effect, and anti-diabetic effect. The aim of this study was to evaluate anti-obesity effect of Pueriaria lobata extract (PLE), and elucidate the effect of it on gene expression related to lipid metabolism. Method : The experiments were performed with the use of ovariectomized rats as estrogen-deficient obesity model. They were grouped NC (normal control), OC (estrogen-deficient control), PLH (100mg/kg of PLE), PLL (20mg/kg). PLE was orally administered for 6 weeks. Body weights and serum lipid level were estimated, and real-time PCR was performed to investigate the effect of PLE on gene expression in liver. Results : PLE decreased the body weight and serum cholesterol and triglyceride, but increased HDL-cholesterol. And PLE increased leptin, CYP27, CPT1, CYP8B1, ACAT2, LDLR, and SCD1, but reduced $PPAR{\gamma}$, PGC1A, HMG-CoA-R, ACAT1, SCD1, and APoB gene expression in liver tissue of rat with estrogen-deficient obesity. Conclusion : It is concluded that Pueriaria lobata reduced body weight, and its effect was expressed by regulation of gene expression related to lipid metabolism in rats with estrogen-deficient obesity.

• Archives of Pharmacal Research
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• v.28 no.12
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• pp.1365-1375
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• 2005

The antiestrogenic effects of marijuana smoke condensate (MSC) and three major cannabinoids, i.e., $\bigtriangleup^{9}$-tetrahydrocannabinol (THC), cannabidiol (CBD), and cannabinol (CBN), were evaluated using in vitro bioassays, viz., the human breast cancer cell proliferation assay, the recombinant human estrogen receptor (ER) competitive binding assay, and the reporter gene assay. The inhibitory effects on estrogen were also examined using the ethoxyresorufin-O­deethylase (EROD) assay, the aromatase assay, and the 17$\beta$-estradiol ($E_{2}$) metabolism assay. The results showed that MSC induced the antiestrogenic effect via the ER-mediated pathway, while THC, CBD, and CBN did not have any antiestrogenic activity. This suggests that the combined effects of the marijuana smoke components are responsible for the antiestrogenicity of marijuana use. In addition, MSC induced the CYP1A activity and the $E_{2}$ metabolism, but inhibited the aromatase activity, suggesting that the antiestrogenic activity of MSC is also related to the indirect ER-dependent pathway, as a result of the depletion of the in situ $E_{2}$ level available to bind to the ER. In conclusion, pyrogenic products including polycyclic aromatic hydrocarbons (PAHs) in the non-polar fraction, which is the most biologically active fraction among the seven fractions of MSC, might be responsible for the antiestrogenic effect.