• BMB Reports
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• 제43권5호
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• pp.305-310
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• 2010

Syndecans, cell surface heparansulfate proteoglycans, have been proposed to act as cell surface receptors and/or coreceptors to play critical roles in multiple cellular functions. However, recent reports suggest that the function of syndecans can be further extended through shedding, a cleavage of extracellular domain. Shedding constitutes an additional level for controlling the function of syndecans, providing a means to attenuate and/or regulate amplitude and duration of syndecan signals by modulating the activity of syndecans as cell surface receptors. Whether these remaining cleavage products are still capable of functioning as cell surface receptors to efficiently transduce signals inside of cells is not clear. However, shedding transforms cell surface receptor syndecans into soluble forms, which, like growth factors, may act as novel ligands to induce cellular responses by association with other cell surface receptors. It is becoming interestingly evident that shed syndecans also contribute significantly to syndecan functions in cancer biology. This review presents current knowledge about syndecan shedding and its functional significance, particularly in the context of cancer.

• BMB Reports
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• 제43권2호
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• pp.91-96
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• 2010

The function of macrophage inhibitory cytokine-1 (MIC-1) in cancer remains controversial, and its signaling pathways remain poorly understood. In this study, we demonstrate that MIC-1 induces the transactivation of EGFR, ErbB2, and ErbB3 through the activation of c-Src in SK-BR-3 breast cells. MIC-1 induced significant phosphorylation of EGFR at Tyr845, ErbB2 at Tyr877, and ErbB3 at Tyr1289 as well as Akt and p38, Erk1/2, and JNK mitogen-activated protein kinases (MAPKs). Treatment of SK-BR-3 cells with MIC-1 increased the phosphorylation level of Src at Tyr416, and induced invasiveness of those cells. Inhibition of c-Src activity resulted in the complete abolition of MIC-1-induced phosphorylation of the EGFR, ErbB2, and ErbB3, as well as invasiveness and matrix metalloproteinase (MMP)-9 expression in SK-BR-3 cells. Collectively, these results show that MIC-1 may participate in the malignant progression of certain cancer cells through the activation of c-Src, which in turn may transactivate ErbB-family receptors.

• BMB Reports
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• 제38권6호
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• pp.709-716
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• 2005

Apoptosis and necrosis are distinguished by modality primarily. Here we show an apoptosis occurred instantly, induced by $300\;{\mu}M$ W-7 ((N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride), inhibitor of calmodulin), which demonstrated necrotic modality. As early as 30 min after W-7 addition, apoptotic (sub-diploid) peak could be detected by fluorescence-activated cell sorter (FACS), “DNA ladders” began to emerge also at this time point, activity of caspase-3 elevated obviously within this period. Absence of mitochondrial membrane potential (MMP) reduction and cytochrome c, AIF (apoptosis inducing factor) release, verified that this rapid apoptosis did not proceed through mitochondria pathway. Activation of caspase-12 and changes of other endoplasmic reticulum (ER) located proteins ascertained that ER pathway mediated this necrosis-like apoptosis. Our findings suggest that it is not credible to judge apoptosis by modality. Elucidation of ER pathway is helpful to comprehend the pathology of diseases associated with ER stress, and may offer a new approach to the therapy of cancer and neurodegenerative diseases.

• 대한한의학회지
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• 제29권4호
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• pp.1-12
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• 2008

Background and Objectives: Sinusitis is a common disease in the otorhinolaryngology field. It is inflammatory change of the mucous membrane which surrounds the sinus. The aim of this study was to investigate the anti-inflammatory effects of the Taklisodok-eum (TSE) extract on the mouse model with acute sinusitis induced by S. pneumoniae. Methods: Thirty six-week-old male BALB/c mice were divided into three groups: the normal group, the group inoculated with S. pneumoniae which caused allergic rhinitis (control group), and the group treated with the TSE extract after it was treated the same as the control group (sample group). Results: $NF-{\kappa}B$ activation was suppressed, and iNOS & COX-2 production were inhibited by TSE in acute sinusitis. Apoptosis was increased by TSE in acute sinusitis. The number of eosinophils in the sample group noticeably decreased when compared to the control group. In the general morphologic change, the increase of damaged respiratory ciliated epithelia & eosinophils' infiltration was lessin the sample group. Goblet cells were maintained in the sample group. MMP-9, HSP-70 and BrdU decreased in the sample group. Apocrine secretion decreased in the sample group. Conclusion: The findings in this study show that TSE reduces acute sinusitis through its anti-inflammatory effects, such as the inhibition of $NF-{\kappa}B$ activity.

• 대한한방부인과학회지
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• 제21권2호
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• pp.59-75
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• 2008

Purpose: This study was performed to determine the inhibitory effect of Polygonum multiflorum(PM) on melanin synthesis in B16F10. Methods: The Inhibitory effects of Polygonum multiflorum(PM) on melanin synthesis were determined by in-vitro assay. To elucidate inhibitory effects of Polygonum multiflorum on melanin synthesis, we determined the melanin release and melanin production in B16F10. And to investigate the action mechanism, we assessed the gene expression of tyrosinase, TRP-1, TRP-2, MMP-2, PKA, PKC, ERK-1 ERK-2, AKT-1, MITF in B16F10. Results: 1. PM inhibited melanin-release, melanin production in B16F10. 2. PM inhibited tyrosinase activity in vitro and in B16F10. 3. PM suppressed the expression of tyrosinase, TRP-1 in B16F10. 4. PM suppressed the expression of PKA in B16F10. 5. PM suppressed the expression of ERK-1, ERK-2, AKT-1 in B16F10. 6. PM suppressed the expression of MITF in B16F10. Conclusion: From these results, it may be concluded that PM possesses the antimelanogenetic effects.

• Toxicological Research
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• 제31권1호
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• pp.33-40
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• 2015

Bee venom (BV) has long been used in traditional Eastern and Western medicine for chronic inflammation, pain and skin therapy. Human exposure to BV, however, often causes unwanted adverse effects and is even fatal in some cases. Phospholipase $A_2$ ($PLA_2$) of BV is now suspected to play a key role in these adverse effects. We investigated the potential use of $PLA_2$-free bee venom (PBV) as a replacement for BV in cosmetic products. PBV prepared by molecular weight cut-off ultrafiltration exhibits a superior profile in comparison with regular BV, by inhibiting elastase activity and suppressing the induction of nitric oxide (NO) and metalloproteinase-9 (MMP-9), while retaining the effects of cell proliferation and protection against ultraviolet B (UVB)-induced damage in human dermal fibroblast cells. PBV thus appears to be more promising than BV as a cosmetic ingredient with a reduced potential for adverse reactions in the recipient.

• 생약학회지
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• 제46권4호
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• pp.295-302
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• 2015

Cynanchi wilfordii Radix roots have been utilized as traditional medicine for variety of diseases including diabetes mellitus, aging progression and scavenging free radicals, enhancing immunity, reducing high serum cholesterol, and anti-tumor activity. However, the mechanisms underlying this effect remain poorly understood. The principal objective of this study was to determine the effect of cynandione A on osteoclast cells. Thus, we was isolated cynandione A from Cynanchi wilfordii Radix roots and evaluated the effect of cynandione A on receptor activator of nuclear factor-${\kappa}B$ ligand (RANKL)-induced osteoclast differentiation. We found that cynandione A significantly inhibited osteoclast differentiation stimulated-RANKL in RAW 264.7 cells. Cynandione A conspicuously inhibited the mRNA and protein expression of matrix metallopeptidase 9 (MMP-9), tartrate-resistant acid phosphatase (TRAP) in cynandione A treated with RANKL. Taken together, our results demonstrated that Cynanchi Wilfordii Radix may be useful treatment option of bone-related disease such as osteoporosis leads to fracture of bone and rheumatoid arthritis.

• 동의생리병리학회지
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• 제19권6호
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• pp.1647-1655
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• 2005

Gamimahaenggamsuk-tang (GMHGST) is used for treatment of inflammatory diseases including rheumatoid arthritis (RA). Here, regulatory activity of GMHGST on RA-mediated inflammatory responses was investigated in cultured human fiDroblast-like synoviocytes (FLS), Levels of mRNAs encoding for inflammatory cytokines such as $IL-1{\beta}$, IL-6 and IL-8 and NOS-II enzyme, which had been induced by $TNF-{\alpha}$ and $IL-1{\beta}$ cotreatment, were decreased to the similar levels as those in cells treated with anti-inflammatory agent MTX. mRNA expressions of matrix metalloproteinase-3 (MMP-3) and tissue inhibitor of metalloproteinases (TIMPs) as well as intercellular adhesion molecule (ICAM) were also downregulated by increasing doses of GMHGST in activated FLS. Moreover, GMHGST appeared to protect cells by decreasing NO levels, and inhibited cell proliferation which had been induced by inflammatory stimulation by $TNF-{\alpha}$ and IL-1. These results suggest that GMHGST is effective as an inhibitory agent for regulating inflammatory responses in activated FLS.

• Journal of Microbiology and Biotechnology
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• 제24권7호
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• pp.914-920
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• 2014

Triple-negative breast cancer (TNBC) possesses a higher rate of distant recurrence and a poorer prognosis than other breast cancer subtypes. Interestingly, most of the heat shock protein 90 (Hsp90) client proteins are oncoproteins, and some are closely related to unfavorable factors of TNBC patients. 17-Demethoxy-reblastatin (17-DR), a novel non-benzoquinone-type geldanamycin analog, exhibited potent Hsp90 ATPase inhibition activity. In this study, the anticancer effects of 17-DR on TNBC MDA-MB-231 cells were investigated. These results showed that 17-DR inhibited cell proliferation, induced apoptosis, and suppressed cell invasion and migration in the MDA-MB-231 cells. Down-regulation of the key Hsp90-dependent tumor-driving molecules, such as RIP1 and MMP-9, by 17-DR may be related to these effects. Taken together, our results suggest that 17-DR has potential as a therapeutic agent for the treatment of TNBC.

• 동의생리병리학회지
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• 제23권1호
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• pp.63-75
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• 2009

The aim of this study was to elucidate the antimelanogenic effect of Dokhwalkisaeng-tang(Duohujisheng-tang) in B16F10 melanoma cells. Dokhwalkisaeng-tang(DKT) was used to develop the effective prescription of inhibition of melanin production. We determined inhibitory effects of DKT on melanin-release, melanin production, and tyrosinase activity in B16F10 melanoma cells. And to explicate the action-mechanism of DKT, melanin-related gene expressions were determined using RT-PCR and real time RT PCR technique in B16F10 melanoma cells. DKT inhibited melanin-release, melanin production in B16F10 melanoma cells considerably. DKT inhibited tyrosinase activity in vitro and in B16F10 melanoma cells. DKT inhibited the expression of tyrosinase, TRP-1, TRP-2 in B16F10 melanoma cells. DKT inhibited the expression of PKA, PKC, MMP-2 and MITF in B16F10 melanoma cells. On the other hand, DKT increased the expression of ERK-1, ERK-2, AKT-1 in B16F10 melanoma cells. From these results, we propose that DKT may have effect on the antimelanogenesis.