• Journal of Ginseng Research
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• v.47 no.2
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• pp.246-254
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• 2023

Background: Here, we aimed to assess the inhibitory effect of a new compound from Panax ginseng on the migration of human ovarian cancer cells and tube formation of human umbilical vein endothelial cells (HUVECs). Methods: A new compound, ginsenglactone A (1), was isolated from ginseng roots, together with seven known compounds (2-8). Spectroscopic data were used to elucidate the chemical structure of 1. The tubular structure formation in HUVECs was assessed by Mayer's hematoxylin staining. The migration of A2780 cells was evaluated using the scratch wound healing assay. Results: HUVECs treated with 1 had the statistically significant decrease in tubular structure formation compared to the HUVECs treated with compounds 2-8. This effect was enhanced by co-treatment with inhibitors for phosphatidylinositol 3-kinase (PI3K) (LY294002) and extracellular signal-regulated kinase (ERK) (U0126). Treatment with 1 decreased the expression of phosphorylation of ERK, PI3K, vascular endothelial growth factor receptor2 (VEGFR2), Akt, and mammalian target of rapamycin (mTOR). In addition, the ability of A2780 cells to cover the scratched area were also decreased. This effect was enhanced by co-treatment with U0126. Lastly, treatment with 1 decreased the phosphorylation of ERK, matrix metalloproteinase-9 (MMP-9), and MMP-2. Conclusion: These results suggest that ginsenglactone A is a potential inhibitor of HUVEC tubular structure formation and A2780 cellular migration, which may be helpful for understanding its anticancer mechanism.

• The Journal of Internal Korean Medicine
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• v.38 no.4
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• pp.409-418
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• 2017

In Korea, Rhus verniciflua Stokes is used to purge hardness, alleviate blood stasis, and treat cancer. However, the mechanisms of related anti-cancer activity are not fully understood in human cancer cells. This study investigated the anti-cancer effects and mechanisms of Rhus verniciflua Stokes on MDA-MB-231 human breast cancer cells and found that treatment with a Rhus verniciflua Stokes extract resulted in time- and concentration-responses that indicated growth inhibition of breast cancer cells by induced apoptosis. This was followed by a decrease in mitochondrial membrane potential; the activation of caspase-3, -8, and -9; and the up-regulation of tBid. Caspase-dependent apoptosis was induced through the inhibition of phosphatidylinositol 3-kinase (PI3K) and the Akt signaling pathway. This study provides evidence that Rhus verniciflua Stokes might be useful for the treatment of breast cancer.

• Journal of Life Science
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• v.23 no.11
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• pp.1397-1403
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• 2013

Fructus Sophorae, the dried ripe fruit of Styphnolobium japonicum (L.), is an herbal ingredient used in traditional Oriental medicine. This study was carried out to investigate the effects of Fructus Sophorae extracts (FSE) on immune modulation in a murine RAW 264.7 macrophage model. As immune response parameters, the production of prostaglandin $E_2$ ($PGE_2$) and tumor necrotic $factor-{\alpha}$ ($TNF-{\alpha}$) were evaluated. Our data revealed that FSE increased the macrophage activation and the production of $PGE_2$ and $TNF-{\alpha}$, which was consistently correlated with upregulation of cyclooxygenase-2 (COX-2) and $TNF-{\alpha}$ expression at both transcriptional and translational levels. On comparative cytokine protein array, FSE significantly increased several cytokines, which was associated with phosphorylation of mitogen- activated protein kinases (MAPKs), including extracellular signal-regulated kinase (ERK), p38 MAPK and c-Jun N-terminal kinase (JNK), and Akt in RAW 264.7 cells. However, each inhibitor of these molecules attenuated the FSE-induced $PGE_2$ production. These results indicate that FSE activated macrophages through the activation of MAPKs and phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathways in RAW 264.7 macrophages. These findings suggest that FSE may provide a promising source of an immunoenhancing agent.

• Journal of Gastric Cancer
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• v.13 no.3
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• pp.129-135
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• 2013

Gastric cancer is the second leading cause of cancer-related deaths worldwide. In advanced and metastatic gastric cancer, the conventional chemotherapy with limited efficacy shows an overall survival period of about 10 months. Patient specific and effective treatments known as personalized cancer therapy is of significant importance. Advances in high-throughput technologies such as microarray and next generation sequencing for genes, protein expression profiles and oncogenic signaling pathways have reinforced the discovery of treatment targets and personalized treatments. However, there are numerous challenges from cancer target discoveries to practical clinical benefits. Although there is a flood of biomarkers and target agents, only a minority of patients are tested and treated accordingly. Numerous molecular target agents have been under investigation for gastric cancer. Currently, targets for gastric cancer include the epidermal growth factor receptor family, mesenchymal-epithelial transition factor axis, and the phosphatidylinositol 3-kinase-AKT-mammalian target of rapamycin pathways. Deeper insights of molecular characteristics for gastric cancer has enabled the molecular classification of gastric cancer, the diagnosis of gastric cancer, the prediction of prognosis, the recognition of gastric cancer driver genes, and the discovery of potential therapeutic targets. Not only have we deeper insights for the molecular diversity of gastric cancer, but we have also prospected both affirmative potentials and hurdles to molecular diagnostics. New paradigm of transdisciplinary team science, which is composed of innovative explorations and clinical investigations of oncologists, geneticists, pathologists, biologists, and bio-informaticians, is mandatory to recognize personalized target therapy.

• Molecules and Cells
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• v.23 no.2
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• pp.198-206
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• 2007

Hydroquinone is a toxic compound and a major benzene metabolite. We report that it strongly inhibits the activation of macrophages and associated cells. Thus, it suppressed the production of proinflammatory cytokines [tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-$1{\beta}$, IL-3, IL-6, IL-10, IL-12p40, IL-23], secretion of toxic molecules [nitric oxide (NO) and reactive oxygen species (ROS)] and the activation and expression of CD29 as judged by cell-cell adhesion and surface staining experiments. The inhibition was due to the induction of heme oxygenase (HO)-1 in LPS-activated macrophages, since blocking HO-1 activity with ZnPP, an HO-1 specific inhibitor, abolished hydroquinone's NO inhibitory activity. In addition, hydroquinone and inhibitors (wortmannin and LY294002) of the phosphatidylinositol-3 kinase (PI3K)/Akt pathway had very similar inhibitory effects on LPS-induced and CD29-mediated macrophage responses, including the phoshorylation of Akt. Therefore, our data suggest that hydroquinone inhibits macrophage-mediated immune responses by modulating intracellular signaling and protective mechanisms.

• Biomedical Science Letters
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• v.29 no.4
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• pp.242-248
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• 2023

Platelets are activated at the sites of vascular injury by a number of molecules, including adenosine diphosphate, collagen and thrombin. The full platelet aggregation is absolutely essential for the normal hemostasis. Glycyrrhiza glabra is a well-known medicinal herb that grows in various parts of the world and is known to have various effects such as antioxidant, anti-inflammatory, anti-atherogenic, anti-osteoporotic and skin-whitening. However, the platelet inhibitory effect of Glycyrrhiza glabra extract (GGE) has not been identified. In this study, we investigated if GGE inhibited platelet aggregation. We observed that GGE inhibited collagen-induced platelet aggregation, Ca²⁺ mobilization, and thromboxane A2 generation. In addition, GGE suppressed phosphorylation of phosphatidylinositol-3 kinase (PI3K), Akt and elevated phosphorylation of inositol 1,4,5-trisphosphate receptor (IP3R), vasodilator stimulated phosphoprotein (VASP). Taken together, GGE showed strong antiplatelet effects and may be used to block platelet-mediated cardiovascular diseases.

• Journal of Life Science
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• v.31 no.1
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• pp.1-9
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• 2021

Brown seaweeds have been shown to decrease blood glucose levels and improve insulin sensitivity previously. In this study, we investigated the effect of fucoidan, a complex polysaccharide derived from brown seaweeds, on glucose uptake to improve insulin resistance, and examined its mechanism of action in 3T3-L1 adipocytes. We observed that fucoidan significantly increased glucose uptake and it was related to an increased expression of plasma membrane-glucose transporter 4 (PM-GLUT4) in 3T3-L1 adipocytes. Fucoidan treatment increased the activation of phosphatidylinositol-3-kinase (PI3K) and the phosphorylation of insulin receptor substrate 1 (IRS1tyr) compared with that of the control cells. Fucoidan also promoted the phosphorylation of Akt and protein kinase C (PKC)-λ/ζ compared to that of the control cells. Moreover, fucoidan significantly upregulated acetyl-CoA-carboxylase (ACC) and adenosine monophosphate - activated protein kinase (AMPK) phosphorylation. As a result, translocation of GLUT4 was significantly enhanced in 3T3-L1 adipocytes, which significantly promoted glucose uptake via the PI3K/AMPK pathways. The elevation of glucose uptake by fucoidan was blocked by inhibitor of PI3K and inhibitor of AMPK in 3T3-L1 adipocytes. These findings indicate that fucoidan might ameliorate glucose uptake through GLUT4 translocation to the plasma membrane by activating the PI3K/Akt and AMPK pathways in 3T3-L1 adipocytes. Fucoidan is thought to be of high material value to diabetes treatments and functional foods.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.46 no.4
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• pp.384-392
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• 2013

An ethanolic extract of Undaria pinnatifida was fractionated using several solvents. Of the fractions, the ethyl acetate fraction had the greatest inhibitory effect on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7 macrophage cells. Using this fraction (U. pinnatifida ethyl acetate extract, UPE), we investigated the molecular mechanism underlying its inhibitory effect on LPS-stimulated RAW 264.7 cells. Pretreatment of the cells with up to $100{\mu}g/mL$ UPE significantly inhibited NO production and inducible nitric oxide synthase (iNOS) expression, in a dose-dependent manner. Similarly, UPE treatment markedly reduced the production of pro-inflammatory cytokines, such as interleukin (IL)-1, IL-6 and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), while it strongly suppressed the nuclear translocation of nuclear factor-kappa B (NF-${\kappa}B$) by preventing proteolytic degradation of inhibitor of nuclear factor ${\kappa}B$ $(I{\kappa}B)-{\alpha}$. Moreover, UPE treatment significantly reduced the phosphorylation of phosphatidylinositol 3-kinase (PI3K)/Akt and mitogen-activated protein kinase (MAPK) in LPS-stimulated cells. These results indicate that UPE contains anti-inflammatory compounds and suggest that it might be used as a functional food material that assists in prevention of inflammatory diseases.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.10
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• pp.4161-4168
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• 2015

Colorectal cancer (CRC) is a worldwide health problem, being the third most commonly detected cancer in males and the second in females. Rising CRC incidence trends are mainly regarded as a part of the rapid 'Westernization' of life-style and are associated with calorically excessive high-fat/low-fibre diet, consumption of refined products, lack of physical activity, and obesity. Most recent epidemiological and clinical investigations have consistently evidenced a significant relationship between obesity-driven inflammation in particular steps of colorectal cancer development, including initiation, promotion, progression, and metastasis. Inflammation in obesity occurs by several mechanisms. Roles of imbalanced metabolism (MetS), distinct immune cells, cytokines, and other immune mediators have been suggested in the inflammatory processes. Critical mechanisms are accounted to proinflammatory cytokines (e.g. IL-1, IL-6, IL-8) and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$). These molecules are secreted by macrophages and are considered as major agents in the transition between acute and chronic inflammation and inflammation-related CRC. The second factor promoting the CRC development in obese individuals is altered adipokine concentrations (leptin and adiponectin). The role of leptin and adiponectin in cancer cell proliferation, invasion, and metastasis is attributable to the activation of several signal transduction pathways (JAK/STAT, mitogen-activated protein kinase (MAPK), phosphatidylinositol 3 kinase (PI3K), mTOR, and 5'AMPK signaling pathways) and multiple dysregulation (COX-2 downregulation, mRNA expression).

• Journal of Veterinary Clinics
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• v.26 no.1
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• pp.8-16
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• 2009

The production of reactive oxygen species (ROS) and nitric oxide (NO) by anticancer agents in rat polymorphonuclear leukocytes (PMN) was examined. PMN treated for short term (< or = 4 h) with cyclophosphamide, cisplatin, tamoxifen and doxifluridine, respectively, exhibited an enhanced respiratory burst upon formylmethionylleucy1-phenylalanine (FMLP) stimulation. In the long term (> 4h), the production of ROS was suppressed in a concentration-dependent manner. The production of superoxide anion (${O_2}^-$) from the FMLP-stimulated PMN was enhanced by the treatment (for 1 hr) of cyclophosphamide, cisplatin, tamoxifen and doxifluridine, respectively. While 1 hr-treatment with cyclophosphamide, cisplatin, tamoxifen, and doxifluridine, respectively, suppressed the production of NO from the FMLP-stimulated PMN, while 8 hr-treatment enhanced the production of NO. Neomycin suppressed chemiluminescence in cisplatin-, tamoxifen- and doxifluridine-pretreated PMN, however near suppression of chemiluminescence by ethanol and genistein was observed in PMN pretreated with these agents. Staurosporine and bisindolylmaleimide suppressed chemiluminescence in cisplatin- and doxifluridine- pretreated PMN. Wortmannin has shown a slight suppression in cyclophosphamide-, cisplatin- and tamoxifen-pretreated PMN, but a strong suppression in doxifluridine-pretreated PMN. Methionine strongly suppressed in cyclophosphamide and cisplatin-pretreated PMN. In conclusion, these results indicate that long term treatment of PMN with cisplatin and doxifluridine inhibit respiratory burst through protein kinase C (PKC) translocation, phospholipase C (PLC), D (PLD) and tyrosine phosphorylation kinase (TPK) activation. Tamoxifen inhibits respiratory burst through PLC, PLD, TPK. Cyclophosphamide inhibits respiratory burst through myeloperoxidase (MPO) activity.