• Journal of Applied Biological Chemistry
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• v.65 no.2
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• pp.93-99
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• 2022

Lysosome organelle extract (LOE) was derived from egg whites. The lysosome is an intracellular organelle that contains several hydrolysis enzymes. Previous studies have reported that LOE performs important functions, such as melanin de-colorization and anti-melanin production in B16F10 melanoma cells. However, its principal molecular and cellular mechanisms have not been elucidated till date. In non-cytotoxic conditions, LOE significantly inhibited α-MSH induced melanin synthesis of murine B16F10 cells. The anti-melanogenic activity of LOE was mediated by suppressing the mRNA expression of tyrosinase enzyme, tyrosinase related protein-1/2 (TRP-1/2), and microphthalmia-associated transcription factor (MITF) genes. By performing western blot analysis, we found that LOE significantly attenuated melanogenesis. In this case, LOE helped in increasing extracellular receptor kinase (ERK) phosphorylation in α-MSH induced B16F10 cells. Furthermore, MITF is found to be a key regulatory transcription factor in melanin synthesis; it was down-regulated by LOE through ERK phosphorylation. In this experiment, PD98059 (MEK inhibitor) was used to check whether LOE directly regulated the activity of ERK. Although LOE exerted inhibitory effect on melanin synthesis, we could not observe this effect in PD98059-treated α-MSH induced B16F10. These results strongly indicate that LOE is related to ERK activation and MITF degradation in anti-skin pigmentation. Hence, LOE should be utilized as a whitening agent of skin in the near future.

• BMB Reports
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• v.55 no.9
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• pp.459-464
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• 2022

Various mechanisms have been suggested to explain the chemopreventive and tumor-inhibitory effects of melatonin. Despite the growing evidence supporting melatonin-induced mitochondrial dysfunction, it remains largely unknown how this phenomenon modulates metabolic reprogramming in cancer cells. The aim of our study was to identify the mechanism underlying the anti-proliferative and apoptotic effects of melatonin, which is known to inhibit glycolysis. We analyzed the time-dependent effects of melatonin on mitochondrial respiration and glycolysis in liver cancer cells. The results showed that from a cell bioenergetic point of view, melatonin caused an acute reduction in mitochondrial respiration, however, increased reactive oxygen species production, thereby inhibiting mTORC1 activity from an early stage post-treatment without affecting glycolysis. Nevertheless, administration of melatonin for a longer time reduced expression of c-Myc protein, thereby suppressing glycolysis via downregulation of HK2 and LDHA. The data presented herein suggest that melatonin suppresses mitochondrial respiration and glycolysis simultaneously in HCC cells, leading to anti-cancer effects. Thus, melatonin can be used as an adjuvant agent for therapy of liver cancer.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2022.09a
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• pp.20-20
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• 2022

Herein, we demonstrate that butein (1) can prevent swelling in a murine lymphedema model by suppressing tumor necrosis factor α (TNF-α) production. Butein derivatives were synthesized and evaluated to identify compounds with in vitro anti-inflammatory activity. Among them, 20 µM of compounds 7j, 7m, and 14a showed 50% suppression of TNF-α production in mouse peritoneal macrophages after lipopolysaccharide stimulation. Compound 14a, exhibited the strongest potency with an in vitro IC₅₀ of 14.6 µM and suppressed limb volume by 70% in a murine lymphedema model. The prodrug strategy enabled a six-fold increase in kinetic solubility of compound 1 and five-fold higher levels of active metabolite in the blood for compound 14a via oral administration in the pharmacokinetics study. We suggest that the compound 14a could be developed as a potential therapeutic agent targeting anti-inflammatory activity to alleviate lymphedema progression.

• Nutrition Research and Practice
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• v.17 no.5
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• pp.844-854
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• 2023

BACKGROUND/OBJECTIVES: Fucoidan, a polysaccharide content in brown algae, has been reported to inhibit the growth of cancer cells. The present study aimed to investigate the suppression effects of fucoidan on A549 non-small cell lung cancer cells migration. MATERIALS/METHODS: The anti-migratory activity of fucoidan in A549 cells was examined by wound healing assay and phalloidin-rhodamine staining in response to fucoidan (0-100 ㎍/mL) treatment for 48 h. Western blot analysis was performed to clarify the protein expressions relevant to migratory activity. RESULTS: Fucoidan (25-100 ㎍/mL) significantly suppressed A549 cells migration together with reduced the intensity of phalloidin-rhodamine which detect filopodia and lamellipodia protrusions at 48 h of treatment. The protein expression indicated that fucoidan significantly suppressed the phosphorylation of focal adhesion kinase (FAK), Src, and extracellular signal-related kinase (ERK). In addition, the phosphorylation of p38 in A549 cells was found to be increased. CONCLUSIONS: Our data conclude that fucoidan exhibits anti-migratory activities against lung cancer A549 cells mediated by inhibiting ERK1/2 and FAK-Src pathway.

• YAKHAK HOEJI
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• v.43 no.2
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• pp.214-220
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• 1999

Present study was aimed to examine whether indomethacin affected the production of NO in the rat paw exudate by carrageenin. Paw edema and nitrite/nitrate levels in the paw exudate were maximal after 4 h and remained elevated up to 10 h, whereas indomethacin (10 mg/kg, po) significantly inhibited the carrageenin-induced paw edema and levels of nitrate in the paw exudate. However, paw edema and nitrite/nitrite levels were increased thereafter for 10 h. Indomethacin also enhanced the expression of iNOS mRNA and protein 4 h after carrageenin infection. Indomethacin inhibited the level of $PGE_2$ in the paw exudate in a time-dependent manner. These results suggest the possibility that indomethacin may potentiate expression of iNOS and subsequently increase nitrite/nitrate level in the late phase of carrageenin-induced rat paw inflammation possibly by suppressing cycloxygenase activity.

• BMB Reports
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• v.46 no.10
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• pp.490-494
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• 2013

The phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a tumor-suppressing lipid phosphatase that is frequently absent in breast tumors. Thus, the stability of PTEN is essential for tumor prevention and therapy. The ubiquitin-proteasome pathway has an important role in regulating the functions of PTEN. Specifically, carboxyl terminus Hsp70-interacting protein (CHIP), the E3 ubiquitin ligase of PTEN, can regulate PTEN levels. In this study, we report that BCL-2-associated athanogene 5 (BAG5), a known inhibitor of CHIP activity, reduces the degradation of PTEN and maintains its levels via an ubiquitylation-dependent pathway. BAG5 is identified as an antagonist of cell tumorigenicity.

• CELLMED
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• v.3 no.1
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• pp.6.1-6.6
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• 2013

Asthma is a chronic inflammatory disease of the lungs, characterized by increased sensitivity to bronchoconstriction associated with infiltration of immune cells and mucus hyper secretion. In South Africa, the indigenous plant Siphonochilus aethiopicus, is used by traditional health practitioners to treat colds and flu, wheezing of the chest, coughs, influenza, sinus problems and mild asthma. In this study we aimed to investigate the potential anti-inflammatory and immune-modulating properties of S. aethiopicus in vitro. The dried and powdered S. aethiopicus plant material was extracted with organic solvents. The dried extracts were screened in vitro in the transcription response, NF-${\kappa}B$ and a cytokine assay. Significant activity was observed for organic extracts of the plant in these assays. This study provides evidence that S. aethiopicus has anti-inflammatory and immune-suppressing properties in vitro. These findings may support anecdotal accounts of its effectiveness against allergic asthma.

• YAKHAK HOEJI
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• v.42 no.5
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• pp.540-543
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• 1998

The nitric oxide (NO) produced in large amounts by inducible nitric oxide synthase is known to be responsible for the vasodilation and hypotension observed in septic shock. We have found that 8-epi-xanthatin from Xanthium strumarium L. inhibited the production of NO in LPS-activated RAW 264.7 cells ($IC_{50}$ value was 1.5 ${\mu}$M). This activity was resulted from the suppressing of inducible nitric oxide synthase enzyme expression.

• Journal of Microbiology
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• v.37 no.4
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• pp.243-247
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• 1999

Effects of divalent cations on self-splicing inhibition by the antibiotic spectinomycin of the phage T4 thymidylate synthase intron (td) have been investigated. $Ca^{2+}$ ion at 1mM concentration suppressed splicing inhibition of spectinomycin by 10% and 50 ${\mu}M\;Co^{2+}$ ion also suppressed splicing inhibition of specinomycin by 10%. $Mg^{2+}$ ion at 6 mM concentration decreased splicing inhibition of spectinomycin by 42% while $Mn^{2+}$ ion decreased the splicing inhibition by 10%. $Zn^{2+}$ ion at 10 uM concentration lowered the splicing inhibition by spectinomycin of 15%. Of all divalent cations tested, $Mg^{2+}$ ion was the most effective in suppressing splicing inhibition by specinomycin whereas $Ca^{2+}$ ion was the least effective. The results suggest that spectinomycin may interact with specific and functional $Mg^{2+}$-binding sites within intron RNA that lead to a displacement of $Mg^{2+}$ essential for catalytic activity.

• Journal of Ginseng Research
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• v.20 no.2
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• pp.154-158
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• 1996

To investigate the protective effect of Korean red ginseng (RG) against oxidative damage, rats were intoxicated by carbon tetrachloride and liver tissues and blood were taken and analyzed histopathologically and biochemically. Light microscopy of the liver showed that RG prevented the necrosis of hepatocytes remarkably and reduced the change of fat. RG increased the capability for serum to suppress oxygen radical in the generating system. It is suggested that RG enhanced the antioxidative potential of the body against $CCl_4$, which would prevent the necrosis of hepatocytes in vivo.