• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.3
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• pp.819-825
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• 2003

pharbitis nil and Taraxacum mongolicum are representative herbs that have been used for cancer treatment in Korean traditional medicine. To understand the molecular basis of the antitumor function, we analyzed the effect of these herbs on proliferation and apoptosis of tumor cells using a gastric cancer cell line AGS. Cell counting assay showed that pharbitis nil strongly inhibit cell proliferation Of AGS whereas Taraxacum mongolicum exhibit no detectable effect on cellular growth. [³H]thymidine uptake analysis also demonstrated that DNA replication of AGS is suppressed in a dose-dependent manner by treatment with pharbitis nil. Additionally, tryphan blue exclusion assay showed that Pharbitis nil induce apoptotic cell death of AGS in a dose-dependent. To explore whether anti antiproliferative and/or proapototic property of Pharbitis nil is associated with their effect on gene expression, we performed RT-PCR analysis of cell cycle- and apoptosis-related genes. Interestingly, mRNA expression levels of c-Jun, c-Fos, c-Myc, and Cyclin D1 were markedly reduced by Pharbitis nil. Taraxacum mongolicum also showed inhibitory action on expression of these growth-promoting protooncogene but there effects are less significant, as compared to Pharbitis nil. Furthermore, it was also found that Pharbitis nil activates expression of the p53 tumor suppressor and its downstream effector p21Waf1, which induce G1 cell cycle arrest and apoptosis. Collectively, our data demonstrate that Pharbitis nil induce growth inhibition and apoptosis of human gastric cancer cells and these effects are accompanied with down-and up-regulation of growth-regulating protooncogenes and tumor suppressor genes, respectively. This observation thus suggests that the anticancer effect of Pharbitis nil might be associated with its regulatory capability of tumor-related gene expression.

• Journal of Microbiology and Biotechnology
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• v.16 no.1
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• pp.84-91
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• 2006

A Saccharomyces cerevisiae pgs1 nulI mutant, which is deficient with phosphatidyl glycerol (PG) and cardiolipin (CL) biosynthesis, grows well on most fermentable carbon sources, but fails to grow on non-fermentable carbon sources such as glycerol, ethanol, and lactate. This mutant also cannot grow on galactose medium as the sole carbon source. We found that the incorporation of $[^{14}C]-galactose$, which is the first step of the galactose metabolic pathway (Leloir pathway), into the pgs 1 null mutant cell was extremely repressed. Exogenously expressed PGS1 (YCpPGS1) under indigenous promoter could completely restore the pgs1 growth defect on non-fermentable carbon sources, and dramatically recovered $[^{14}C]-galactose$ incorporation into the pgs1 mutant cell. However, PGS1 expression under the GALl promoter $(YEpP_{GAL1}-PGS1myc)$ could not complement pgs1 mutation, and the GAL2-lacZ fusion gene $(YEpP_{GAL2}-lacZ)$ also did not exhibit its $\beta-galactosidase$ activity in the pgs1 mutant. In wild-type yeast, antimycin $A(1\;{\mu}g/ml)$, which inhibits mitochondrial complex III, severely repressed not only the expression of the GAL2-lacZ fusion gene, but also uptake of $[^{14}C]-galactose$. However, exogenously expressed PGS1 partially relieved these inhibitory effects of antimycin A in both the pgs1 mutant and wild-type yeast, although it could not basically restore the growth defect on galactose by antimycin A. These results suggest that the PGSI gene product has an important role in utilization of galactose by Gal genes, and that intact mitochondrial function with PGS1 should be required for galactose incorporation into the Leloir pathway. The PGS1 gene might provide a clue to resolve the historic issue about the incapability of galactose with deteriorated mitochondrial function.

• The Korean Journal of Zoology
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• v.33 no.2
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• pp.141-151
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• 1990

Raf protein kinases and protein kinase C belong to serine/threonine-specific proteins in the cytoplasin, and are similar to each other in functional structure and the aspect of the distribution of celI. The distribution of raf protein kinase in the cerebrum of Geoclemys reevesfi as studied by using the antibodies against a-raf and c-raf protein kinase which induce the expression of raf fainily oncogenes. In general, raf protein kinases were distributed in such restricted regions as the general pallium, hippocampal formation, pdmordiuin hippocampi,nucleus of lateral olfactory tract, basal amygdaloid nucleus, and bed of stria terminalis. Immunological labeling of c-raf protein kinase was more widespread than that of a-raf. However, the intensity of the labeling of c-raf was lower than that of a-raf. The spherical cells of basal amygdaloid nucleus is a ring-like form, because only the cytoplasm was imunolabeled. Especially, c-raf protein kinase occurred in the cells which contained protein kinase C abundandy such as pyramidal cells and Purkinje cells. This suggests that a- and e-raf protein kinases may synegistically induce carclnoma with myc gene which is activated by protein kinase C.

• Radiation Oncology Journal
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• v.21 no.3
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• pp.227-237
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• 2003

Purpose: The human chronic myelogenous leukemia cell line, K562, expresses the chimeric bcr-abl oncoprotein, whose deregulated protein tyrosine kinase activity antagonizes via DNA damaging agents. Previous experiments have shown that nanomolar concentrations of herbimycin A (HWA) coupled with X-irradiation have a synergistic effect in inducing apoptosis in the Ph-positive K562 leukemia cell line, but genistein, a PTK inhibitor, is non selective for the radiation-induced apoptosils on $p210^{bcr/abl}$ protected K562 cells. In these experiments, the cytoplasmic signal transduction pathways, the Induction on a number of transcription factors and the differential gene expression in this model were investigated. Materials and Methids: K562 cells in the exponential growth phase were used in this study. The cells were irradiated with 0.5-12 Gy, using a 6 Mev Linac (Clinac 1800, Varian, USA). Immediately after irradiation, the cells were treated with $0.25/muM$ of HMA and $25/muM$ of genistein, and the expressions and the activities of abl kinase, MAPK family, NF- kB, c-fos, c-myc, and thymidine kinase1 (TK1) were examined. The differential gene expressions induced by PTK inhibitors were also investigated. Results: The modulating effects of herbimycin A and genistein on the radiosensitivity of K562 cells were not related to the bcr-abl kinase activity. The signaling responses through the MAPK family of proteins, were not involved either in association with the radiation-induced apoptosis, which is accelerated by HMA, the expression of c-myc was increased. The combined treatment of genistein, with irradiation, enhanced NF- kB activity and the TK1 expression and activity. Conclusion: The effects of HMA and genistein on the radiosensitivity on the K562 cells were not related to the bcr-abl kinase activity in this study, another signaling pathway, besides the WAPK family responses to radiation to K562 cells, was found. Further evaluation using this model will provide valuable information for the optional radiosensitization or radioprotection.

• Journal of Microbiology and Biotechnology
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• v.33 no.3
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• pp.398-409
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• 2023

LncRNAs play crucial roles in the progression of colon adenocarcinoma (COAD), but the role of LINC01232 in COAD has not received much attention. The present study was designed to explore the related mechanisms of LINC01232 in the progression of COAD. LINC01232, miR-181a-5p, p53, c-myc, Bcl-2, cyclin D1, p16, Bax, VEGF, E-cadherin, vimentin, N-cadherin and SDAD1 expressions were determined by western blot and qRT-PCR. CCK-8, tubule formation, and Transwell assays were employed to detect proliferation, angiogenesis, and migration/invasion of COAD cells, respectively. The relationship between LINC01232 and miR-181a-5p was predicted by LncBase Predicted v.2, and then verified through dual luciferase reporter gene assay. According to the results, LINC01232 was highly expressed in COAD cells and enhanced proliferation, angiogenesis, migration, and invasion of COAD cells. Downregulated LINC01232 promoted expression of p53 and p16, and inhibited c-myc, Bcl-2 and cyclin D1 expressions in COAD cells, while upregulation of LINC01232 generated the opposite effects. LINC01232 was negatively correlated with miR-181a-5p while downregulated miR181a-5p could reverse the effects of siLINC01232 on cell proliferation, angiogenesis, migration, and invasion. Similarly, miR-181a-5p mimic could also offset the effect of LINC01232 overexpression. SiLINC01232 increased the expressions of Bax and E-cadherin, and decreased the expressions of VEGF, vimentin, N-cadherin and SDAD1, which were partially attenuated by miR-181a-5p inhibitor. Collectively, LINC01232 enhances the proliferation, migration, invasion, and angiogenesis of COAD cells by decreasing miR-181a-5p expression.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.1
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• pp.167-173
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• 2005

To investigate the possible molecular mechanism (s) of bee venom as a candidate of anti-cancer drug, we examined the effects of the compound on the growth of human lung carcinoma cell line A549. Bee venom treatment declined the cell growth and viability of A549 cells in a concentration-dependent manner, which was associated with induction of apoptotic cell death. Bee venom down-regulated the levels of anti-apoptotic genes such as Bcl-2 and Bcl-XS/L, however, the levels of Bax, a pro-apoptotic gene, were up-regulated. Bee venom treatment induced not only tumor suppressor p53 but also cyclin-dependent kinase inhibitor p21WAF1/CIP1 expression in a dose-dependent manner. Furthermore, bee venom treatment induced the down-regulation of telomerase reverse transcriptase mRNA and telomeric repeat binding factor expression of A549 cells, however, the levels of telomerase-associated protein-1 and c-myc were not affected. Taken together, these findings suggest that bee venom-induced inhibition of human lung cancer cell growth is associated with the induction of apoptotic cell death via regulation of several major growth regulatory gene products, and bee venom may have therapeutic potential in human lung cancer.

• The Journal of Korean Obstetrics and Gynecology
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• v.23 no.2
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• pp.71-84
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• 2010

Purpose: In the theory of traditional medicine, Glenditsia spina(GS) can resolve carbuncle, relive swelling, dispel wind and destroy parasites. This study was designed to investigate the effects of GS on gene expression of ovarian tissue in polycystic ovary syndrome(PCOS) rats. Methods: In this experiment, female rats injected with a single dose of 2 mg estradiol valerate(EV) and GS was given for 5 weeks. The genetic profile for the effects on ovarian tissue in PCOS rats was measured using microarray technique, and the functional analysis on these genes was conducted. Results: 985 genes were increased in control and restored to normal level in GS group. (B), 733 genes were decreased in control group and restored to normal level in GS group. (F). Metabolic pathways related in B group genes were Graft-versus-host disease, Allograft rejection, Autoimmune thyroid disease, Cytokine-cytokine receptor interaction, Small cell lung cancer, Type I diabetes mellitus. Metabolic pathways related in F group genes were Antigen processing and present, Adipocytokine signalling pathway, Focal adhesion, ECM-receptor interaction, Pancreatic cancer, Notch signalling pathway, Tight junction. The network of total protein interactions was measured using cytoscape program, and some key molecules, such as c-Fos, c-Myc, ABL1 related in B group, MAPK8, RASA1, CALR related in F group that can be used for elucidation of therapeutical mechanism of medicine in future were identified. Conclusion: These results suggest possibility of GS as anti-cancer and anti-hyperplasia drug in PCOS. In addition, the present author also suggests that related mechanisms are involved in suppression of proto-oncogene such as c-Fos, c-Myc and ABL1, and in regulation of cell cycle such as RASA1.

• Korean Journal of Environmental Biology
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• v.36 no.2
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• pp.131-139
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• 2018

The warming of water as a result of climate change affects fish habitat. Variations in water temperature affect fish physiology almost totally. The rise in water temperature due to climate change leads to hypoxia following decreased oxygen solubility and decreased binding capacity of oxygen-carrying hemoglobin. This study was conducted to evaluate the health status of Atlantic salmon (Salmo salar) fry at elevated water temperatures($20^{\circ}C$) compared with optimum water temperature ($15^{\circ}C$). The method facilitated the detection of biomarker genes using NGS RNAseq analysis and evaluation of their expression pattern using RT-qPCR analysis. The biomarker genes included interferon alpha-inducible protein 27-like protein 2A transcript variant X3, protein L-Myc-1b-like, placenta growth factor-like transcript variant X1, fibroblast growth factor receptor-like 1 transcript variant X1, transferrin, intelectin, thioredoxin-like, c-type lectin lectoxin-Thr1-like, ladderlectin-like and calponin-1. The selected biomarker genes were sensitive to changes in water temperature based on NGS RNAseq analysis. The expression patterns of these genes based on RT-qPCR were similar to those of NGS RNAseq analysis.

• Toxicological Research
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• v.17
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• pp.83-88
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• 2001

Most reactive oxygen species (ROS) are free radicals and implicated in the development of a number of disease processes including artherosclerosis, neurodegenerative disorders, aging and cancer. ROS are byproducts of a number of in vivo metabolic processes and are formed deliberately as part of nor-mal inflammatory response. On the other hand, ROS are generated either as by products of oxygen reduction during xenobiotic metabolism or are liberated as the result of the futile redox cycling of the chemical agents including several chemical carcinogens. A better understanding of the mechanisms of free radical toxicity may yield valuable clue to risks associated with chemical exposures that leading to the development of chronic diseases including cancer. The molecular biology of ROS-mediated alterations in gene expression, signal transduction and carcinognesis is one of the important subjects in free radical toxicology. Epidemiological studies suggest that high intake of vegetables and fruits are associated with the low incidence of human cancer. Many phytopolyphenols such as tea polyphenols, curcumin, resveratrol, apigenin, genistein and other flavonoids have been shown to be cancer chemopreventive agents. Most of these compounds are strong antioxidant and ROS scavengers in vitro and effective inducers of antioxidant enzymes such as superoxide dismutatse, catalase and glutathione peroxidase in vivo. Several cellular transducers namely receptor tyrosine kinase, protein kinase C, MAPK, PI3K, c-jun, c-fos, c-myc, NFkB, IkB kinase, iNOS, COX-2, Bcl-2, Bax, etc have been shown to be actively modulated by phyto-polyphenols. Recent development in free radical toxicology have provided strong basis for understanding the action mechanisms of cancer chemoprevention.

• Journal of Nutrition and Health
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• v.30 no.8
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• pp.987-994
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• 1997

To investigate the effects of n-3 fatty acids on breast cancer, MDA-MB231 human breast cancer cells were cultured in the presence of $\alpha$-linolenic (LNA), eicosapentaenoic(EPA), and docosahexaenoic acid (DHA) at a concentration of 0.5$\mu\textrm{g}$/ml in serum -free IMM medium. Cell growth was monitored and thiobarbituric acid reactive substances (TBARS), $\alpha$-tocopherol contents, and oncogene expression were measured. To compare the effects of n-3 fatty acids with other types of fatty acid, steraic (STA), olieic(OA). linoleic acid(LA) were used. After one day , cell growth was retarded most highly when DHA was in the medium. Cellular TBARS level measured after three days of culture was the highest with DHA in the medium and was also increased by LNA and EPA, compared with STA, OA and LA. Alpha-tocoopherol contents of cells were decreased by DHA but only modestly. There was non significant difference in $\alpha$-tocopherol contents in cells cultured in the presence of the other fatty acids. northern blot hybridization carried out with cells cultured during 24 hours showed that levels of erbB-2 mRNA were not altered by six different fatty acids in the medium but those of c-myc were transiently decreased in the early period by both n-6 and n-3 polyunsaturated fatty acids. The level of tumor suppressor gen p53 mRNA , however, was increased by DHA with time. It is concluded that the cytotoxicity of lipid peroxide and increased expression of tumor suppressor gene p53 are at least partly responsible for the inhibitory effect of DHA on growth of breast cancer cells.