• Journal of Food Hygiene and Safety
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• v.31 no.4
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• pp.294-298
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• 2016

Natural products are attractive as the source of new drug development. Especially, numerous unknown marine bioresources are an object of attention because the ocean occupies three fourth of the earth. Survival of marine bioresources in extreme environment may induce the production of biological active compounds. As previous study, we examined over 40 specimens of marine sponges collected from Micronesia and screened their anti-proliferative activities in various cancer cell lines. Among them, we investigated Coscinoderma sp.'s activity and mechanism in human colon carcinoma HCT116 and RKO cells. Furthermore, we also used the p53-knockout of HCT116 cells and the p53 loss of RKO cells for elucidating the role of p53. Coscinoderma sp. inhibited cellular viability independently of the p53 status. Therefore, we compared the expression level of cell death-related proteins by Coscinoderma sp. in HCT16 and in HCT116 p53KO cells. Coscinoderma sp. increased p53 level and NOXA levels and induced apoptosis under the condition of p53 existence. On the other hand, Coscinoderma sp. increased p21 and mTOR levels in HCT116 p53KO cells. These results suggest that Coscinoderma sp. induced anti-proliferation effect through different pathway depending on p53 status.

• Journal of Pharmacopuncture
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• v.21 no.1
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• pp.18-25
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• 2018

Objective: D-galactose (D-gal) is well-known agent to induce aging process. In the present study, we selected crocin, the main constituent of Crocus sativus L. (saffron), against D-gal- induced cytotoxicity in human neuroblastoma SH-SY5Y cells. Methods: Pretreated cells with crocin ($25-500{\mu}M$, 24 h) were exposed to D-gal (25-400 mM, 48 h). The MTT assay was used for determination cell viability. Dichlorofluorescin diacetate assay (DCF-DA) and senescence associated ${\beta}$-galactosidase staining assay (SA-${\beta}$-gal) were used to evaluate the generation of reactive oxygen species and beta-galactosidase as an aging marker, respectively. Also advanced glycation end products (AGEs) expression which is known as the main mechanism of age-related diseases was measured by western blot analysis. Results: The findings of our study showed that treatment of cells with D-gal (25-400 mM) for 48h decreased cell viability concentration dependency. Reactive oxygen species (ROS) levels which are known as main factors in age-related diseases increased from $100{\pm}8%$ in control group to $132{\pm}22%$ in D-gal (200 mM) treated cells for 48h. The cytotoxic effects of D-gal decreased with 24h crocin pretreatment of cells. The cell viability at concentrations of $100{\mu}M$, $200{\mu}M$ and $500{\mu}M$ increased and ROS production decreased at concentrations of 200 and $500{\mu}M$ to $111.5{\pm}6%$ and $108{\pm}5%$, respectively. Also lysosomal biomarker of aging and carboxymethyl lysine (CML) expression as an AGE protein, significantly increased in D-gal 200 mM group after 48h incubation compare to control group. Pre-treatment of SHSY-5Y cells with crocin ($500{\mu}M$) before adding D-gal significantly reduced aging marker and CML formation. Conclusion: Treatment of SH-SY5Y cells with crocin before adding of D-gal restored aging effects of D-gal concentration dependency. These findings indicate that crocin has potent anti- aging effects through inhibition of AGEs and ROS production.

• Biomolecules & Therapeutics
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• v.31 no.1
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• pp.73-81
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• 2023

Sirtuins (SIRTs) belong to the nicotinamide adenine dinucleotide (NAD+)-dependent class III histone deacetylase family. They are key regulators of cellular and physiological processes, such as cell survival, senescence, differentiation, DNA damage and stress response, cellular metabolism, and aging. SIRTs also influence carcinogenesis, making them potential targets for anticancer therapeutic strategies. In this study, we investigated the anticancer properties and underlying molecular mechanisms of a novel SIRT1 inhibitor, MHY2251, in human colorectal cancer (CRC) cells. MHY2251 reduced the viability of various human CRC cell lines, especially those with wild-type TP53. MHY2251 inhibited SIRT1 activity and SIRT1/2 protein expression, while promoting p53 acetylation, which is a target of SIRT1 in HCT116 cells. MHY2251 treatment triggered apoptosis in HCT116 cells. It increased the percentage of late apoptotic cells and the sub-G1 fraction (as detected by flow cytometric analysis) and induced DNA fragmentation. In addition, MHY2251 upregulated the expression of FasL and Fas, altered the ratio of Bax/Bcl-2, downregulated the levels of pro-caspase-8, -9, and -3 proteins, and induced subsequent poly(ADP-ribose) polymerase cleavage. The induction of apoptosis by MHY2251 was related to the activation of the caspase cascade, which was significantly attenuated by pre-treatment with Z-VAD-FMK, a pan-caspase inhibitor. Furthermore, MHY2251 stimulated the phosphorylation of c-Jun N-terminal kinase (JNK), and MHY2251-triggered apoptosis was blocked by pre-treatment with SP600125, a JNK inhibitor. This finding indicated the specific involvement of JNK in MHY2251-induced apoptosis. MHY2251 shows considerable potential as a therapeutic agent for targeting human CRC via the inhibition of SIRT1 and activation of JNK/p53 pathway.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.1
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• pp.347-350
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• 2012

TP53 is the mostly commonly mutated gene in many cancers and the P53 tumor suppressor protein is involved in multiple cellular processes, including transcription, DNA repair, genomic stability, senescence, cell cycle control and apoptosis. A common single nucleotide polymorphism located within the proline rich region of TP53 gene at codon 72 in exon 4 encodes either proline or arginine. TP53 Arg 72 is more active than TP53 Pro 72 in inducing apoptosis. The aim of this study was to understand the association of the 72 codon polymorphism with acute leukemia development and prognosis. A total of 288 acute leukemia cases comprising 147 acute lymphocytic leukemia (ALL) and 141 acute myeloid leukemia (AML), as well as 245 controls were recruited for analysis of the TP53 72 polymorphism using PCR-RFLP method. Significant association of homozygous arginine genotype with AML was observed (${\chi}^2$- 133.53; df-2, p < 0.001. When data were analyzed with respect to clinical variables, elevation in mean WBC, blast %, LDH levels and slight reduction in DFS in ALL cases with the arginine genotype was observed. In contrast, AML patients with Pro/Pro had elevated WBC, Blast%, LDH levels with slightly reduced DFS. Our study indicates that Arg/Arg genotype might confer increased risk to development of acute myeloid leukemia.

• Journal of Microbiology and Biotechnology
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• v.28 no.1
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• pp.59-64
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• 2018

Listeria monocytogenes can asymptomatically inhabit the human intestine as a commensal bacterium. However, the mechanism by which L. monocytogenes is able to inhabit the intestine without pathogenic symptoms remains unclear. We compared the invasion efficiency of L. monocytogenes strains with the 268- and 385-bp-long actA gene. Clinical strains SMFM-CI-3 and SMFM-CI-6 with 268-bp actA isolated from patients with listeriosis, and strains SMFM-SI-1 and SMFM-SI-2 with the 385-bp gene isolated from carcasses, were used for inoculum preparation. The invasion efficiency of these strains was evaluated using Caco-2 cells (intestinal epithelial cell line), prepared as normal and healthy cells with tightened tight junctions and senescent cells with loose tight junctions that were loosened by adriamycin treatment. The invasion efficiency of L. monocytogenes strains with the 268-bp-long actA gene was 1.1-2.6-times lower than that of the strains with the 385-bp-long gene in normal and healthy cells. However, the invasion efficiency of both types of strains did not differ in senescent cells. Thus, L. monocytogenes strains with the 268-bp-long actA gene can inhabit the intestine asymptomatically as a commensal bacterium, but they may invade the intestinal epithelial cells and cause listeriosis in senescent cells.

• Proceedings of the Korean Society of Developmental Biology Conference
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• 2003.10a
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• pp.111-111
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• 2003

Telomeres are the end of chromosomes and consist of a tandem repeat sequence of (TTAGGG)n and associated proteins. Telomerase is a ribonucleoprotein which act as a template for the synthesis of telomeric DNA. Telomeres are essential for chromosome stability and are related with cell senescence, apoptosis and cancer. Even though telomeres and telomerase have been studied extensively, very little is known about telomere dynamics in embryonic cells. This study was carried out to analyze the telomeres distribution and telomerase activity of chicken cells during embryonic and developmental stages. The target cells for analysing were sperms, ovulated ova, early embryonic cells and the cells from brain, heart, liver, kidney and germinal tissue in fetus. Telomeres distribution on target cells was analyzed by Q-FISH (Quantitation-Fluorescence in situ Hybridization) techniques using a chicken telomere repeat probe. Telomerase activity was performed by TRAP assay (Telomeric repeat Amplification Protocol) with target DNA. In results, the telomeres of chicken were found at the ends of all chromosomes. In addition, chicken had interstitial telomeres on chromosomes 1, 2 and 3. Telomerase activity was highly detectable in early embryonic cells, germinal tissues and kidney cells. Whereas telomerase activity was gradually down-regulated when the organs, including brain, heart, and liver, were developed from embryos. In the distribution of telomeric DNA on the embryonic and developmental stages, most of the cells was gradually decreased in telomere quantity during ontogenesis.

• Proceedings of the Korea Society of Poultry Science Conference
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• 2004.11a
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• pp.13-15
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• 2004

Telomeres are the end of chromosomes and consist of a tandem repeat sequence of (TTAGGG)n and associated proteins. Telomeres are essential for chromosome stability and are related with cell senescence and apoptosis. This study was carried out to analyze the amount of telomeric DNA of chicken lymphocytes, which is to considered as bio-marker. The amount of telomeric DNA of lymphocytes in Korean Native Chicken and White Leghorn was analyzed by quantitative-fluorescence in situ hybridization (Q-FISH) technique using the chicken telomeric DNA probe. Telomere quantifies were compared among breeds, ages and sex, and the relationship between the amount of telomeres and their productive trait was also analyzed. Comparing the amount of telomeric DNA on lymphocytes during growing period, the amount of telomeres was gradually decreased as growing older. The telomere quantity was also significantly different in breeds and sex. Estimating correlation coefficient, the amount of telomeres was positively correlated to sexual maturity and body weight but negatively correlated to hen day egg production and egg weight. These results implicate the telomere quantity is considered as an individual bio-marker.

• Plant Biotechnology Reports
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• v.5 no.1
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• pp.27-34
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• 2011

Jasmonates control diverse plant developmental processes, such as seed germination, flower, fruit and seed development, senescence and tuberization in potato. To understand the role of methyl jasmonate (MeJA) in potato tuberization, the Arabidopsis JMT gene encoding jasmonic acid carboxyl methyltransferase was constitutively overexpressed in transgenic potato plants. Increases in tuber yield and size as well as in vitro tuberization frequency were observed in transgenic plants. These were correlated with JMT mRNA level-- the higher expression level, the higher the tuber yield and size. The levels of jasmonic acid (JA), MeJA and tuberonic acid (TA) were also higher than those in control plants. Transgenic plants also exhibited higher expression of jasmonate-responsive genes such as those for allene oxide cyclase (AOC) and proteinase inhibitor II (PINII). These results indicate that JMT overexpression induces jasmonate biosynthesis genes and thus JA and TA pools in transgenic potatoes. This results in enhanced tuber yield and size in transgenic potato plants.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3437-3441
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• 2012

Background: Oncogenic Bmi-1 (B-lymphoma Moloney murine leukemia virus insertion region-1) belongs to the Polycomb-group (PcG) family of proteins and plays an important role in the regulation of proliferation, senescence, cell cycle and apoptosis, chromosome stability, activation of gene transcription. Methods: To clarify the roles of Bmi-1 in tumourigenesis and progression of gastric carcinomas, it was examined by immunohistochemistry (IHC) and real-time RT-PCR in gastric carcinomas, dysplasia, intestinal metaplasia (IM), and gastritis with a comparison of its expression with clinicopathological parameters of carcinomas. Results: There was gradually increased Bmi-1 protein expression from gastritis, IM, dyplasia to carcinoma (p<0.001). Bmi-1 expression was positively linked to tumor size, depth of invasion, lymph node metastasis and worse prognosis of carcinomas (p<0.001), but not to age or sex of carcinoma patients (p>0.05). There was higher Bmi-1 protein expression in intestinal-type carcinomas than diffuse-type ones (p<0.001). At mRNA level, Bmi-1 protein expression was increased from gastritis, IM, dysplasia and carcinoma (p<0.001). Bmi-1 overexpression was observed in gastric carcinoma with larger diameter, deeper invasion, lymph node metastasis, and intestinal-type carcinoma (p<0.05). Conclusion: These findings indicate that up-regulated Bmi-1 expression is positively linked to pathogenesis, growth, invasion, metastasis and differentiation of gastric carcinomas. It was considered as a promising marker to indicate the aggressive behaviors and prognosis of gastric carcinomas.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.8
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• pp.4913-4918
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• 2013

Objective: To assess the level of an inpatient population's awareness about hepatitis and primary liver cancer (PLC), the most common type of which is hepatocellular carcinoma (HCC), and then to initiate education of this group. Methods: A survey was conducted with 1300 participants within the inpatient unit in representative tertiary hospitals in the Chaoshan area of China. Structured questionnaires contained demographic data and statements about different aspects of liver cancer and hepatitis. The questionnaires were completed by trained medical practitioners after they had conducted the interviews. Results: One way ANOVA showed that the sample population lacked adequate knowledge about HCC and hepatitis. Stepwise multiple regression analysis demonstrated that the participant's level of education had the greatest impact on their total knowledge score when other variables remained constant. Conclusions: The study demonstrated: a general lack of awareness amongst the participants about the preventative strategies, and the management options available for people with primary liver cancer and hepatitis; education level was an important factor affecting knowledge levels. The demonstrated deficiencies in people's knowledge about hepatitis and HCC, and their lack of subsequent protective behaviours are likely to play an important role in HCC and hepatitis transmission or prevention.