• Asian Pacific Journal of Cancer Prevention
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• 제14권10호
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• pp.5783-5788
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• 2013

Trigonella foenum in graecum (Fenugreek) is a traditional herbal plant used to treat disorders like diabetes, high cholesterol, wounds, inflammation, gastrointestinal ailments, and it is believed to have anti-tumor properties, although the mechanisms for the activity remain to be elucidated. In this study, we prepared a methanol extract from Fenugreek whole plants and investigated the mechanism involved in its growth-inhibitory effect on MCF-7 human breast cancer cells. Apoptosis of MCF-7 cells was evidenced by investigating trypan blue exclusion, TUNEL and Caspase 3, 8, 9, p53, FADD, Bax and Bak by real-time PCR assays inducing activities, in the presence of FME at $65{\mu}g/mL$ for 24 and 48 hours. FME induced apoptosis was mediated by the death receptor pathway as demonstrated by the increased level of Fas receptor expression after FME treatment. However, such change was found to be absent in Caspase 3, 8, 9, p53, FADD, Bax and Bak, which was confirmed by a time-dependent and dose-dependent manner. In summary, these data demonstrate that at least 90% of FME induced apoptosis in breast cell is mediated by Fas receptor-independently of either FADD, Caspase 8 or 3, as well as p53 interdependently.

• Proceedings of the Ginseng society Conference
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• 고려인삼학회 1990년도 Proceedings of International Symposium on Korean Ginseng, 1990, Seoul, Korea
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• pp.36-44
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• 1990

The analgesic effect of morphine was antagonized and the development of tolerance was suppressed by the modification of the neurologic function in the animals treated with ginseng saponins. The activation of the spinal descending inhibitory systems as well as the supraspinal structures by the administration of morphine was inhibited in the animals treated with ginseng saponins intracerebrally or intrathecally The development of morphine tolerance and dependence, and the abrupt expression of naloxone induced abstinence syndrome were also inhibited by ginsenoside Kbl , Rba, Rgl and Re. These results suggest that ginsenoside Kbl, Rba, Rgl and Re are the bioactive components of panax ginseng on the inhibition of the development of morphine tolerance and dependence, and the inhibition of abrupt abstinence syndrome. In addition, further research on the minor components of Panax ginseng should be investigated. A single or daily treatment with ginseng saponins did not induce any appreciable changes in the brain level of monoamines at the various time intervals and at the various day intervals, respectively The inhibitory or facilitated effects of ginseng saponins on electrically evoked contractions in guinea pig ileum (U-receptor) and mouse was definers (5·receptor) were not mediated through opioid receptors. The antagonism of a x receptor agonist, U-, iO.488H was also not mediated through opioid receptors in the animals treated with ginseng saponins, bolt mediated through serotonergic mechanisms. Ginseng saponins inhibited morphine S-dehydrogenase that catalyzed the production of morphine from morphine, and increased hepatic glutathione contents for the detoxification of morphine. This result suggests that the dual action of the above plays an important role in the inhibition of the development of morphine tolerance and dependence.

• BMB Reports
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• 제53권5호
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• pp.284-289
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• 2020

Tamoxifen, a nonsteroidal estrogen receptor (ER) antagonist, is used routinely as a chemotherapeutic agent for ER-positive breast cancer. However, it is also causes side effects, including retinotoxicity. The retinal pigment epithelium (RPE) has been recognized as the primary target of tamoxifen-induced retinotoxicity. The RPE plays an essential physiological role in the normal functioning of the retina. Nonetheless, potential therapeutic agents to prevent tamoxifen-induced retinotoxicity in breast cancer patients have not been investigated. Here, we evaluated the action mechanisms of sulfasalazine against tamoxifen-induced RPE cell death. Tamoxifen induced reactive oxygen species (ROS)-mediated autophagic cell death and caspase-1-mediated pyroptosis in RPE cells. However, sulfasalazine reduced tamoxifen-induced total ROS and ROS-mediated autophagic RPE cell death. Also, mRNA levels of tamoxifen-induced pyroptosis-related genes, IL-1β, NLRP3, and procaspase-1, also decreased in the presence of sulfasalazine in RPE cells. Additionally, the mRNA levels of tamoxifen-induced AMD-related genes, such as complement factor I (CFI), complement factor H (CFH), apolipoprotein E (APOE), apolipoprotein J (APOJ), toll-like receptor 2 (TLR2) and toll-like receptor 4 (TLR4), were downregulated in RPE cells. Together, these data provide novel insight into the therapeutic effects of sulfasalazine against tamoxifen-induced RPE cell death.

• Animal cells and systems
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• 제16권5호
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• pp.376-384
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• 2012

Although ginsenosides have a variety of physiologic or pharmacologic functions in various regions, there are only a few reports on the effects of transient receptor potential melastatin 7 (TRPM7) channels. Here, we showed evidence suggesting that TRPM7 channels play an important role in ginseng total saponin (GTS)-mediated cellular injury. The combination techniques of electrophysiology, pharmacological analysis, small interfering RNA (siRNA) method and cell death assays were used. GTS depolarized the resting membrane potentials and decreased the amplitude of pacemaker potentials in cultured interstitial cells of Cajal (ICCs) in gastrointestinal (GI) tract. The TRPM7-like currents in single ICCs and the overexpressing TRPM7 in HEK293 cells were inhibited by GTS. However, GTS had no effect on $Ca^{2+}$-activated $Cl^-$ conductance. GTS inhibited the survival of human gastric (AGS) and brea (MCF-7) adenocarcinoma cells. Also, GTS inhibited the TRPM7-like currents in AGS and MCF-7 cells. The GTS-mediated cytotoxicity was inhibited by TRPM7-specific siRNA. In addition, we showed that overexpression of TRPM7 channels in HEK293 cells was inhibited by GTS. Thus, TRPM7 channels are involved in GTS-mediated cell death in AGS and MCF-7 cells, and these channels may represent a novel target for physiological disorders where GTS plays an important role.

• YAKHAK HOEJI
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• 제52권2호
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• pp.111-116
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• 2008

Diethylstilbestrol (DESB) is a synthetic estrogen not only that routinely prescribed, but also that known to be a teratogen. In this study, we found a novel pharmacological feature that DESB is able to positively modulate CD29 $({\beta}1-integrin)$ function. Thus, DESB up-regulated homotypic cell-cell adhesion of monocytic U937 cells mediated by CD29. However, DESB did not increase the surface level of CD29 and its binding activity to ligand (fibronectin), according to flow cytometric analysis and cell-fibronectin adhesion assay. Instead, the DESB-mediated up-regulation of cell-cell adhesion was blocked by several signaling enzyme inhibitors. Treatment of U0126 [an extracellular signal-regulated kinase (ERK) inhibitor], SB20358 (a p38 inhibitor) or Rp-8-pCPT-cGMP (a protein kinase G inhibitor) clearly inhibited DESB-mediated up-regulation of cell-cell adhesion induced by CD29. However, estrogen receptor antagonist ICI 182,780 failed to abrogate DESB effect. Therefore, our data suggest that DESB may up-regulate CD29-mediated cell-cell adhesion via modulating intracellular signaling enzymes such as ERK, PKG, and p38, independent of estrogen receptor function.

• Proceedings of the Ginseng society Conference
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• 고려인삼학회 2004년도 추계 학술대회 및 정기총회
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• pp.7-11
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• 2004

We previously reported that ginseng inhibited NMDA receptors in cultured hippocampal neurons. Here, we further examined the detailed mechanism of ginseng-mediated inhibition using its main active ingredient, ginsenoside Rg$_3$. Co-application of ginsenoside Rg$_3$ with increasing concentrations of NMDA did not change the EC$_{50}$ of NMDA to the receptor, suggesting ginsenoside Rg$_3$ inhibits NMDA receptors without competing with the NMDA-binding site. Ginsenoside Rg$_3$-mediated inhibition also occurred in a distinctive manner from the well-characterized NMDA receptor open channel blocker, MK-801, However, ginsenoside Rg$_3$ produced its effect in a glycine concentration-dependent manner and shifted the glycine concentration-response curve to the right without changing the maximal response, suggesting the role of ginsenoside Rg$_3$ as a competitive NMDA receptor antagonist. We also demonstrated that ginsenoside Rg$_3$ significantly protected neurons against NMDA insults. Therefore, these results suggest that ginsenoside Rg$_3$ protects NMDA-induced neuronal death via a competitive interaction with the glycine-binding site of NMDA receptors in cultured hippocampal neurons.

• Proceedings of the Korean Society of Toxicology Conference
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• 한국독성학회 2001년도 International Symposium on Dietary and Medicinal Antimutgens and Anticarcinogens
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• pp.186-186
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• 2001

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an environmental toxin that activates the aryl hydrocarbon receptor (AhR) and disrupts multiple endocrine signaling pathways by enhancing ligand metabolism, altering hormone synthesis, down regulating receptor levels, and interfering with gene transcription. And TCDD-mediated gene transactivation via the AhR has been shown to be dependent upon estrogen receptor (ER) expression in human breast cancer cells.(omitted)

• BMB Reports
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• 제50권7호
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• pp.384-389
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• 2017

The Nogo-B receptor (NgBR) is necessary for not only Nogo-B-mediated angiogenesis but also vascular endothelial growth factor (VEGF) -induced angiogenesis. However, the molecular mechanisms underlying the regulatory role of the VEGF-NgBR axis in angiogenesis are not fully understood. Here, we report that miR-26a serves as a critical regulator of VEGF-mediated angiogenesis through directly targeting NgBR in endothelial cells (ECs). Stimulation of ECs by VEGF increased the expression of NgBR and decreased the expression of miR-26a. In addition, miR-26a decreased the VEGF-induced migration and proliferation of ECs. Moreover, miR-26a overexpression in ECs decreased the VEGF-induced phosphorylation of the endothelial nitric oxide synthase (eNOS) and the production of nitric oxide, which is important for angiogenesis. Overall, these data suggest that miR-26a plays a key role in VEGF-mediated angiogenesis through the modulation of eNOS activity, which is mediated by its ability to regulate NgBR expression by directly targeting the NgBR 3'-UTR.

• Journal of Physiology & Pathology in Korean Medicine
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• 제18권1호
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• pp.110-113
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• 2004

The Baenong-san has long been used for treatment of inflammatory in Korea. In this study, the anti-inflammatory effects of Baenong-san water extract (BWX) were investigated in proteinase-activated receptor-2 (PAR2)-mediated rat paw edema. Paw edema was induced by injection of trypsin or trans-cinnamoyl-LIGRLO-NH₂ (to-NH₂) into hindpaw of rats. BWX (10, 50, 100 and 200mg/kg) was orally administered 1 h before induction of inflammation. At doses of 50, 100 and 200 mg/kg, BWX showed significant inhibition of both change in paw volume and vascular permeability. BWX(100mg/kg) significantly also inhibited PAR2 agonist-induced myeloperoxidase (MPO) activity in paw tissue. This study demonstrated that BWX has an anti-inflammatory action for PAR2-mediated paw edema.

• Journal of Integrative Natural Science
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• 제10권1호
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• pp.7-13
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• 2017

Neuromedin U receptor 1 is a GPCR protein which binds with the neuropeptide, neuromedin. It is involved in the regulation of feeding and energy homeostasis and related with immune mediated inflammatory diseases like asthma. It plays an important role in maintaining the biological clock and in the regulation of smooth muscle contraction in the gastrointestinal and genitourinary tract. Analysing the structural features of the receptor is crucial in studying the pathophysiology of the diseases related to the receptor important. As the three dimensional structure of the protein is not available, in this study, we have performed the homology modelling of the receptor using 5 different templates. The models were subjected to model validation and two models were selected as optimal. These models could be helpful in analysing the structural features of neuromedin U receptor 1 and their role in disorders related to them.