• Korean Journal of Pharmacognosy
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• v.36 no.2 s.141
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• pp.88-92
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• 2005

Apoptosis plays an important role in autoimmune chronic (Hashimoto's) thyroiditis, a disorder that often results in hypothyroidism. The goal of this study was to induce apoptosis by the combination of inflammatory cytokines, interferon $(IFN)-{\gamma}$ and tumor necrosis factor $(TNF)-{\alpha}$, and to investigate a potential role of medicinal plants in the thyroid follicular cells (FRTL) in vitro. The apoptosis was evaluated by cellular viability, DNA fragmentation, and terminal deoxynucleotidyl transferase-mediated deoxy-UTP nick end labeling (TUNEL) assay. Extract of Gamgung-tang (GGT, Glycyrrhizae Radix, black beans, Angelicae Radix, and Cnidii Rhizoma) $(0.3{\sim}9.0mg/ml)$ was shown to maintain the viability of cells treated with $IFN-{\gamma}(100U/ml)$ and $TNF-{\alpha}$ (0.5 ng/ml). FRTL cells were found to undergo DNA fragmentation with the inflammatory cytokines. The extract of GGT inhibited DNA fragmentation in dose-dependent manner. The cells with TUNEL-positive nuclei were detected with $IFN-{\gamma}$ and $TNF-{\alpha}$ treatment. The number of TUNEL-positive cells decreased with the treatment of extract of GGT. These results indicate that medicinal plants inhibit the occurrence of apoptosis in thyroid follicular cells, therefore, may have therapeutic potential in the treatment of autoimmune chronic thyroiditis.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.3
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• pp.623-627
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• 2005

Abnormal thyroid cell proliferation has a very important role in hypothyroidism. Thyroid stimulating hormone (TSH) stimulates proliferation and maintains differentiated function in thyroid follicular cells. A functioning rat thyroid cell line (FRTL) was used to study the effect of Gamgung-tang (GGT, Glycyrrhizae Radix, black beans, Angelicae Radix and Cnidii Rhizoma) on proliferation and cAMP accumulation of thyrocytes. Proliferation of cell was assessed by DNA synthesis and incorporation of $[^3H]thymidine$ into DNA. The concentration of cAMP was measured simultaneously with growth assessment. Extract of GGT ($0.15{\sim}0.9\;mg/ml$ increased DNA synthesis in a dose-dependent manner. GGT at 0.6 (p<0.05) and 0.9 mg/ml (p<0.01) significantly increased $[^3H]thymidine$ incorporation. A comparable effect was observed with TSH. GGT also enhanced cAMP accumulation. These results indicate that GGT increases the proliferation of thyrocytes and may be considered a promising agent for the treatment of autoimmune thyroid disease.

• Journal of Life Science
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• v.8 no.1
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• pp.51-59
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• 1998

The apoptosis-inducing activity of ursolic acid (UA) was examined in mouse F9 teratocarcinoma cells on the bases of biochemical and morphological characteeristics. UA, pentacyclic trierpene acid, exhibits antitumor activities including inhibition of skin tumorigenesis, induction of tumor cell differentiation and antitumor promotion. Treatment with UA showed that the decrease of cell viability was dose-dependent. UA also induced genomic DNA fragmetation, a hallmark of apoptosis, indicating that the mechanism of UA-induced F9 cell death was through apoptosis. When the morphology of the F9 cells was examined by electron microscopy, the cells treated with UA showed the charcteristic morphological features of apoptosis such as chromatin condensation and nuclear fragmentation. DNA fragmentations by UA were inhibired by cycloheximide, which suggest that de novo protein synthesis was required for DNA fragmentation by UA. Inaddition, the expression of c-jun was increased, but those of c-myc and laminin B1 were decreased during apoptosis induced by UA in F9 cells. These results suggest that UA causes an apoptosis in F9 cells. Further, the increased expression of c-jun may be involved in the UA-induced apoptosis of f9 cells.

• Korean Journal of Pharmacognosy
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• v.34 no.3 s.134
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• pp.237-241
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• 2003

This study was carried out to test the growth inhibitory effects of sesamolin obtained from sesame seeds. Sesamolin inhibited the growth of human leukemia HL-60 cells in cultures and the synthesis of macromolecules in dose- and time-dependent manners. Sesamolin in the $60{\sims}100\;{\mu}g/ml$ range was cytostatic. At concentrations greater than $200\;{\mu}g/ml$ sesamolin was cytocidal to HL-60 cells and at $60\;{\mu}g/ml$ inhibited the synthesis of DNA, RNA and protein in HL-60 cells by 35.1, 6.1, and 5.3%, whereas at $200\;{\mu}g/ml$ these inhibitions were 86.8%, 81.5% and 96.7%, respectively. The inhibitory effect of sesamolin on DNA synthesis was irreversible.

• Biomolecules & Therapeutics
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• v.29 no.1
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• pp.90-97
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• 2021

Ultraviolet B (UVB) radiation causes DNA base modifications. One of these changes leads to the generation of 8-oxoguanine (8-oxoG) due to oxidative stress. In human skin, this modification may induce sunburn, inflammation, and aging and may ultimately result in cancer. We investigated whether phloroglucinol (1,3,5-trihydroxybenzene), by enhancing the expression and activity of 8-oxoG DNA glycosylase 1 (Ogg1), had an effect on the capacity of UVB-exposed human HaCaT keratinocytes to repair oxidative DNA damage. Here, the effects of phloroglucinol were investigated using a luciferase activity assay, reverse transcription-polymerase chain reactions, western blot analysis, and a chromatin immunoprecipitation assay. Phloroglucinol restored Ogg1 activity and decreased the formation of 8-oxoG in UVB-exposed cells. Moreover, phloroglucinol increased Ogg1 transcription and protein expression, counteracting the UVB-induced reduction in Ogg1 levels. Phloroglucinol also enhanced the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) as well as Nrf2 binding to an antioxidant response element located in the Ogg1 gene promoter. UVB exposure inhibited the phosphorylation of protein kinase B (PKB or Akt) and extracellular signal-regulated kinase (Erk), two major enzymes involved in cell protection against oxidative stress, regulating the activity of Nrf2. Akt and Erk phosphorylation was restored by phloroglucinol in the UVB-exposed keratinocytes. These results indicated that phloroglucinol attenuated UVB-induced 8-oxoG formation in keratinocytes via an Akt/Erk-dependent, Nrf2/Ogg1-mediated signaling pathway.

• Biomedical Science Letters
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• v.26 no.4
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• pp.288-295
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• 2020

Infection of Helicobacter pylori on gastric mucosa is associated with various gastric diseases. According to the WHO, H. pylori causes gastric cancer and has been classified as a class I carcinogen. Riboflavin is an essential vitamin which presents in a wide variety of foods. Previous studies have shown that riboflavin/UVA was effective against the growth inhibition of Staphylococcus aureus, S. epidermidis and multidrug-resistant Pseudomonas aeruginosa and had the potential for antimicrobial properties. Thus, we hypothesized that riboflavin has a potential role in the growth inhibition of H. pylori. To demonstrate inhibitory concentration of riboflavin against H. pylori, we performed agar and broth dilution methods. As a result, we found that riboflavin inhibited the growth of H. pylori. The MIC was 1 mM in agar and broth dilution test. Furthermore, to explain the inhibitory mechanism, we investigated whether riboflavin has an influence on the replication-associated molecules of the bacteria using RT-PCR to detect mRNA expression level in H. pylori. Riboflavin treatment of H. pylori led to down-regulation of polA and dnaB mRNA expression levels in a dose dependent manner. After then, we also confirmed whether riboflavin has cytotoxicity to human cells. We used AGS, a gastric cancer cell line, and treated with riboflavin did not show statistically significant decrease of cell viability. Thus, these results indicate that riboflavin can suppress the replication machinery of H. pylori. Taken together, these findings demonstrate that riboflavin inhibits growth of H. pylori by inhibiting replication of the bacteria.

• Molecules and Cells
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• v.44 no.2
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• pp.101-115
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• 2021

The INO80 chromatin remodeling complex has roles in many essential cellular processes, including DNA replication. However, the mechanisms that regulate INO80 in these processes remain largely unknown. We previously reported that the stability of Ino80, the catalytic ATPase subunit of INO80, is regulated by the ubiquitin proteasome system and that BRCA1-associated protein-1 (BAP1), a nuclear deubiquitinase with tumor suppressor activity, stabilizes Ino80 via deubiquitination and promotes replication fork progression. However, the E3 ubiquitin ligase that targets Ino80 for proteasomal degradation was unknown. Here, we identified the C-terminus of Hsp70-interacting protein (CHIP), the E3 ubiquitin ligase that functions in cooperation with Hsp70, as an Ino80-interacting protein. CHIP polyubiquitinates Ino80 in a manner dependent on Hsp70. Contrary to our expectation that CHIP degrades Ino80, CHIP instead stabilizes Ino80 by extending its half-life. The data suggest that CHIP stabilizes Ino80 by inhibiting degradative ubiquitination. We also show that CHIP works together with BAP1 to enhance the stabilization of Ino80, leading to its chromatin binding. Interestingly, both depletion and overexpression of CHIP compromise replication fork progression with little effect on fork stalling, as similarly observed for BAP1 and Ino80, indicating that an optimal cellular level of Ino80 is important for replication fork speed but not for replication stress suppression. This work therefore idenitifes CHIP as an E3 ubiquitin ligase that stabilizes Ino80 via nondegradative ubiquitination and suggests that CHIP and BAP1 act in concert to regulate Ino80 ubiquitination to fine-tune its stability for efficient DNA replication.

• The Korean Journal of Physiology and Pharmacology
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• v.9 no.4
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• pp.239-246
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• 2005

In the central nervous system, nitric oxide (NO) is associated with many pathological diseases such as brain ischemia, neurodegeneration and inflammation. The epigallocatechin gallate (EGCG), a major compound of green tea, is recognized as protective substance against neuronal diseases. This study is aimed to investigate the effect of EGCG on NO-induced cell death in PC12 cells. Administration of sodium nitroprusside (SNP), a NO donor, decreased cell viability in a dose- and time-dependent manner and induced genomic DNA fragmentation with cell shrinkage and chromatin condensation. EGCG diminished the decrement of cell viability and the formation of apoptotic morphologenic changes as well as DNA fragmentation by SNP. EGCG played as an antioxidant that attenuated the production of reactive oxygen species (ROS) by SNP. The cells treated with SNP showed downregulation of Bcl-2, but upregulation of Bax. EGCG ameliorated the altered expression of Bcl-2 and Bax by SNP. The release of cytochrome c from mitochondria into cytosol and expression of voltage -dependent anion channel (VDAC)1, a cytochrome c releasing channel in mitochondria, were increased in SNP-treated cells, whereas were attenuated by EGCG. The enhancement of caspase-9, preceding mitochondria-dependent pathway, caspase-8 and death receptor-dependent pathway, as well as caspase-3 activities were suppressed by EGCG. SNP upragulated Fas and Fas-L, which are death receptor assembly, whereas EGCG ameliorated the expression of Fas enhanced by SNP. These results demonstrated that EGCG has a protective effect against SNP-induced apoptosis in PC12 cells, through scavenging ROS and regulating the mitocondria- and death receptor-mediated signal pathway. The present study suggest that EGCG might be a natural neuroprotective substance.

• Journal of the Korean Society of Food Science and Nutrition
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• v.39 no.8
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• pp.1119-1125
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• 2010

To evaluate resveratrol as a prostate cancer preventive material, we investigated its anti-proliferative and apoptotic effects in RC-58T/h/SA#4 primary human prostate cancer cells. Resveratrol significantly decreased the number of viable RC-58T/h/SA#4 cells in a dose- and time-dependent manner. Resveratrol showed cytotoxicity against RC-58T/h/SA#4, LNCaP, PC-3 human prostate cancer cells with $IC_{50}$ values of 245, 320 and $340\;{\mu}M$, respectively. However the cytotoxic potential of resveratrol against normal RWPE-1 cells was lower ($IC_{50}=982\;{\mu}M$). Resveratrol induced cell death as evidenced by the increased formation of apoptotic bodies, nuclear condensation, sub-G1 phase, and DNA fragmentation. Resveratrol activated initiator caspases 8, and 9 as well as effector caspase 3 in a dose-dependent manner. Furthermore, the general caspase inhibitor z-VAD-fmk significantly inhibited resveratrol-induced apoptosis compared to cells without treatment. These results clearly indicate that resveratrol-induced apoptosis was dependent on caspase activation. Further, resveratrol modulated the down regulation of Bcl-2 (anti-apoptotic), and Bid. However, the level of Bax (pro-apoptotic) remained unchanged. These results suggest that resveratrol induced apoptosis in RC-58T/h/SA#4 cells via a mitochondrial-mediated caspase-dependent pathway, suggesting therapeutic potential against prostate cancer.

• Korean journal of applied entomology
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• v.60 no.2
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• pp.255-262
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• 2021

The potato tuber moth, Phthorimaea operculella (Zeller) has been known as a quarantine pest of potato. This study investigated inhibition doses of electron beam irradiation (EBM) by comparing their effects on the development and reproduction and DNA damage of the insect pest. Eggs (0-12 h old), larvae (3^rd and 5^th instar), pupae (less than 1 d old after pupation) and adults (less than 1 d old after emergence) were irradiated with increasing doses of EBM. The EBM with 150 Gy could not completely prevent the hatchability of eggs and pupation of the hatched larvae. The hatchability from the irradiated eggs were 19.3%. However, adult emergence from the irradiated eggs were completely inhibited. When 3^rd and 5^th instar larvae were irradiated at 100 Gy, the adult emergence from the irradiated larvae and the fecundity of the adults were completely inhibited. When pupae and adults were irradiated at 300 Gy and 400 Gy, respectively, the hatchability of the F₁ eggs was completely inhibited. The alkaline comet assay on the level of DNA damage by EBM in P. operculella adults indicates that the EBM increased DNA damage level in a dose-dependent manner, and the damage was repaired in a time-dependent manner. These results may recommend EBM of 150 Gy as a phytosanitary treatment for P. operculella. However further confirmative study is required for the practical application of this EBM dose for P. operculella disinfestation.