Anti-inflammatory effects of 8-hydroxydeoxyguanosine in LPS-induced microglia activation: suppression of STAT3-mediated intercellular adhesion molecule-1 expression

Kim, Dong Hyun; Cho, Ik Hyun; Kim, Hong Sook; Jung, Jae-Chul; Kim, Ja Eun; Lee, Kwang Ho; Park, Taekyu; Yang, Young Mok; Seong, Seung Yong; Ye, Sang‐Kyu; Chung, Myung‐Hee

doi:10.1038/emm.2006.49

Cited by 40 publications

(19 citation statements)

References 40 publications

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“…Of the factors regulated by Stat3 (5), IL-6, VEGF, and NF-κB also in turn promote Stat3 activation or are in cross-talks that perpetuate protumorigenic processes (6,7,26). The present study raises the possibility that sICAM (29), G-CSF, MIF/GIF, Serpine 1, and IL-1RA induction support Stat3-dependent tumor processes, including angiogenesis (30) (Fig. S9); MIF is overexpressed in breast cancer (31) and promotes disease progression (32), Serpine 1 expression correlated with advanced clear cell renal cell carcinoma and promoted tumor angiogenesis and aggressiveness (33).…”

Section: Bp-1-102 Is Detectable At Micromolar Concentrations In Plasmmentioning

confidence: 74%

Orally bioavailable small-molecule inhibitor of transcription factor Stat3 regresses human breast and lung cancer xenografts

Zhang

Yue

Page

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

304

344

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Computer-aided lead optimization derives a unique, orally bioavailable inhibitor of the signal transducer and activator of transcription (Stat)3 Src homology 2 domain. BP-1-102 binds Stat3 with an affinity ( K D ) of 504 nM, blocks Stat3–phospho-tyrosine (pTyr) peptide interactions and Stat3 activation at 4–6.8 μM, and selectively inhibits growth, survival, migration, and invasion of Stat3-dependent tumor cells. BP-1-102–mediated inhibition of aberrantly active Stat3 in tumor cells suppresses the expression of c-Myc, Cyclin D1, Bcl-xL, Survivin, VEGF, and Krüppel-like factor 8, which is identified as a Stat3 target gene that promotes Stat3-mediated breast tumor cell migration and invasion. Treatment of breast cancer cells with BP-1-102 further blocks Stat3–NF-κB cross-talk, the release of granulocyte colony-stimulating factor, soluble intercellular adhesion molecule 1, macrophage migration-inhibitory factor/glycosylation-inhibiting factor, interleukin 1 receptor antagonist, and serine protease inhibitor protein 1, and the phosphorylation of focal adhesion kinase and paxillin, while enhancing E-cadherin expression. Intravenous or oral gavage delivery of BP-1-102 furnishes micromolar or microgram levels in tumor tissues and inhibits growth of human breast and lung tumor xenografts.

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Section: Bp-1-102 Is Detectable At Micromolar Concentrations In Plasmmentioning

confidence: 74%

Orally bioavailable small-molecule inhibitor of transcription factor Stat3 regresses human breast and lung cancer xenografts

Zhang

Yue

Page

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

304

344

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“…STATs (signal transducers and activators of transcription) are cytoplasmic transcription factors which transmit signals to the nucleus and regulate gene expression by binding to the specific target sequence (Joung et al, 2005;Kim et al, 2006a;Yu et al, 2007). Many studies have demonstrated that STAT3 is aberrantly activated in a wide variety of cancers and contributes to cancer progression by upregulating oncogenes such as MMP-9 (Page et al, 2000;Wei et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

LYR71, a derivative of trimeric resveratrol, inhibits tumorigenesis by blocking STAT3-mediated matrix metalloproteinase 9 expression

Kim

Shin

et al. 2008

Exp Mol Med

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Abbreviations: ChIP, chromatin immunoprecipitation; LYR71, 6-methyl-2-propylimino-6, 7-dihydro-5H-benzo [1, 3]-oxathiol-4-one; MMP, matrix metalloproteinase; RANTES, regulated on activation normal T cell expressed and secreted; STAT, signal transducer and activator of transcription AbstractTumor migration/invasion is the main cause of tumor progression and STAT3 is needed to enhance tumor migration/invasion by up-regulating MMP-9. Thus, agents that inhibit STAT3 activation may be used as an anticancer drug. We present herein that 6-methyl-2-propylimino-6, 7-dihydro-5H-benzo [1, 3]-oxathiol-4-one (LYR71) , a derivative of trimeric resveratrol, has an anticancer activity through inhibition of STAT3 activation. We found that LYR71 suppressed STAT3 activation and inhibited the expression and activity of MMP-9 in RANTES-stimulated breast cancer cells. In addition, LYR71 reduced RANTES-induced MMP-9 transcripts by blocking STAT3 recruitment, dissociating p300 and deacetylating histone H3 and H4 on the MMP-9 promoter. Furthermore, LYR71 inhibited tumor migration/invasion in RANTES-treated breast cancer cells and consequently blocked tumor progression in tumor-bearing mice. Taken together, the results of this study suggest that LYR71 can be therapeutically useful due to the inhibition effect of STAT3-mediated MMP-9 expression in breast cancer cells.

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“…Biological activity of the molecule 8OHdG has been demonstrated in murine brain microglial cells and macrophages where it's positive effects include reduction of LPS-induced reactive oxidative species (ROS) and nitric oxide (NO) production, inhibition of Rac1 signaling and reduction of TNF-α, IL-6, and IFN-γ expression (D. H. Kim et al, 2006; H. S. Kim et al, 2006; Lee et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Markers of Oxidative Stress in Human Milk do not Differ by Maternal BMI But are Related to Infant Growth Trajectories

Young

Patinkin

Pyle

et al. 2017

Matern Child Health J

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Objective Obesity in adults is associated with inflammation and oxidative stress. Whether or not this phenotype is reflected in human milk (HM) composition, or may impact infant growth remains unknown. We investigated whether HM from overweight/obese (OW/Ob) mothers exhibited higher concentrations of inflammatory cytokines and markers of oxidative stress. We also correlated these bioactive components with infant growth patterns. Methods This was an observational cohort of 56 breastfeeding mothers and their infants (33 normal weight (NW) and 23 OW/Ob). Infants were followed until 6 months of age and HM collected at 2-weeks and 4-months. Results Markers of oxidative stress, 8-hydroxy-deoxyguanosine (8OHdG) and 4-hydroxynonenol (HNE), decreased in HM over time (p<0.001) and did not differ between NW and OW/Ob women. Concentrations of inflammatory cytokines, IL-6, IL-8, and TNF-α, were all inter-correlated (p<0.001) but did not differ between NW and OW/Ob women. HM fat, protein, lactose, and total calories did not differ between NW and OW/Ob women. Infant growth patterns did not differ by group. In a model of infant weight-for-length-Z score trajectory, there was a significant interaction between both lactose and 8OHdG with maternal group: HM lactose and 8OHdG concentrations were both positively associated with increases in WLZ trajectory only among infants breastfed by OW/Ob mothers. Conclusions for Practice HM composition was relatively stable between NW and OW/Ob women. In exclusively breastfed infants, HM concentrations of lactose and 8OHdG, a marker of oxidative stress, may contribute to regulation of infant weight gain, especially among infants of OW/Ob women.

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Anti-inflammatory effects of 8-hydroxydeoxyguanosine in LPS-induced microglia activation: suppression of STAT3-mediated intercellular adhesion molecule-1 expression

Cited by 40 publications

References 40 publications

Orally bioavailable small-molecule inhibitor of transcription factor Stat3 regresses human breast and lung cancer xenografts

Orally bioavailable small-molecule inhibitor of transcription factor Stat3 regresses human breast and lung cancer xenografts

LYR71, a derivative of trimeric resveratrol, inhibits tumorigenesis by blocking STAT3-mediated matrix metalloproteinase 9 expression

Markers of Oxidative Stress in Human Milk do not Differ by Maternal BMI But are Related to Infant Growth Trajectories

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