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Cyclooxygenase-2 as a Molecular Target for Cancer Chemopreventive Agents
Surh, Young-Joon The Korean Society of Toxicology Korea Environment 2001 Toxicological Research Vol.17 No.-
Recently, considerable attention has been focused on the role of cyclooxygenase-2 (COX-2) in the carcinogenesis as well as in inflammation. Improperly overexpressed COX-2 has been observed in many types of human cancers and transformed cells in culture. Thus, it is conceivable that targeted inhibition of abnormally or improperly up-regulated COX-2 provides one of the most effective and promising strategies for cancer prevention. A ubiquitous eukaryotic transcription factor, NF-kB is considered to be involved in regulation of COX-2 expression. Furthermore, extracellular-regulated protein kinase and p38 mitogen-activated protein (MAP) kinase appear to be key elements of the intracellular signaling cascades involved in NF-kB activation in response to a wide array of external stimuli. Certain chemopreventive phytochemicals suppress activation of NF-kB by blocking one or more of the MAP kinases, which may contribute to their inhibitory effects on COX-2 induction. One of the plausible mechanisms by which chemopreventive phytochemicals inhibit NF-kB activation involves suppression of degradation of the inhibitory unit I kB, which hampers subsequent translocation of p65, the functionally active subunit of NF-kB.
Antioxidant and Anti-inflammatory Activities of Butanol Extract of Melaleuca leucadendron L.
Surh, Jeong-Hee,Yun, Jung-Mi The Korean Society of Food Science and Nutrition 2012 Preventive Nutrition and Food Science Vol.17 No.1
Melaleuca leucadendron L. has been used as a tranquilizing, sedating, evil-dispelling and pain-relieving agent. We examined the effects of M. leucadendron L. extracts on oxidative stress and inflammation. M. leucadendron L. was extracted with methanol (MeOH) and then fractionated with chloroform ($CHCl_3$) and butanol (BuOH). Antioxidant activity of the MeOH extract and BuOH fraction were higher than that of both ${\alpha}$-tocopherol and butyrated hydroxytoluene (BHT). Total phenol content in the extracts of M. leucadendron L., especially the BuOH fraction, well correlated with the antioxidant activity. The anti-inflammatory activity of BuOH extracts were investigated by lipopolysaccharide (LPS)-induced nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$) production, and cyclooxygenase-2 (COX-2) expression in RAW 264.7 macrophages. The BuOH fraction significantly inhibited LPS-induced NO and $PGE_2$ production. Furthermore, BuOH extract of M. leucadendron L. inhibited the expression of COX-2 and iNOS protein without an appreciable cytotoxic effect on RAW264.7 cells. The extract of M. leucadendron L. also suppressed the phosphorylation of inhibitor ${\kappa}B{\alpha}$ ($I{\kappa}B{\alpha}$) and its degradation associated with nuclear factor-${\kappa}B$ (NF-${\kappa}B$) activation. Furthermore, BuOH fraction inhibited LPS-induced NF-${\kappa}B$ transcriptional activity in a dose-dependent manner. These results suggested that M. leucadendron L. could be useful as a natural antioxidant and anti-inflammatory resource.
Surh, H.B.,Jang, Y.Y.,Kim, S.C.,Shim, D.J.,Huh, N.S. Elsevier Science Publishers B.V. (North-Holland) 2017 Theoretical and applied fracture mechanics Vol.90 No.-
<P>In this study, the approximate estimates of elastic-plastic J and COD for thin-walled pipes with axial through-wall cracks (TWCs) and high strain hardening exponents under internal pressure are developed based on the GE/EPRI and enhanced reference stress (ERS) methods. For the estimations based on the GE/EPRI method, the proposed tabulated plastic influence functions for fully plastic J and COD are derived from three-dimensional finite element(FE) analyses. On the basis of these plastic influence functions, an optimized reference load (which plays an important role in the ERS method) is newly suggested. Finally, the present elastic-plastic J and COD estimations are verified by comparing the predicted results with the FE results using actual tensile behavior of SA312 type 304 SAW stainless steel. The estimations based on both GE/EPRI and ERS methods provide better approximations for thin-walled pipes with axial TWC and high strain hardening exponent, than do the existing estimations. The importance of the elastic plastic fracture mechanics assessment, using the present solutions for thin-walled pipe with axial TWC and high strain hardening exponent, are also discussed. (C) 2017 Elsevier Ltd. All rights reserved.</P>
Surh, Young-Joon 이화여자대학교 세포신호전달연구센터 2009 고사리 세포신호전달 심포지움 Vol. No.11
The induction of antioxidant enzyme gene expression represents the first line of cellular defence against oxidative/nitrosative stress and other noxious stimuli. Experimental models of various diseases including acute inflammation, atherosclerosis, neurodegenerative disorders and cancer have demonstrated that the induction of heme oxygenase-1(HO-1) can prevent or mitigate the symptoms associated with these ailments. Nuclear factor E2-related factor-2(Nrf2) has been identified as a major transcription factor responsible for regulating expression of HO-1 and other antioxidant enzymes. Our recent studies have demonstrated that peroxynitrite induces HO-1 expression and subsequently glutamate cysteine ligase(GCLC) through activation of Nrf2 signaling, which confers the cellular protection or tolerance against the subsequent injuries. HO-1 induction was also associated with cytoprotection against inflammatory tissue injuries. Some chemopreventive and chemoprotective phytochemicals, such as curcumin, zerumbone, resveratrol, the green tea polyphenol EGCG, sulforaphane and capsaicin, induce HO-1 expression via Nrf2 activation. Nrf2 knock out mice were less responsive to HO-1 induction following administration of some of these phytochemicals and more prone to inflammatory as well as oxidative or nitrosative stress. Recent studies have revealed that cysteine thiols present in Keap1, a negative regulator of Nrf2, function as redox sensors in fine-tuning of transcriptional regulation of Nrf2. Certain chemopreventive and cytoprotective agents as well as electrophiles and prooxidants can oxidize or covalently modify critical cysteine thiols present in Keap1, thereby diminishing the affinity of Keap1 for Nrf2. This leads to release of Nrf2 for translocation to nucleus where it binds to antioxidant response elements, potentiating cellular defence signaling.