• Proceedings of the Korean Society of Toxicology Conference
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• 2002.05a
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• pp.95-95
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• 2002

Cyclooxygenases (COXs) are key enzymes in the conversion of arachidonic acid into prostanoids, which are involved in cell proliferation and inflammation. Two distinct COXS have been identified: COX-l which is constitutively expressed and COX-2 which is induced by different products such as tumor promoters or growth factors.(omitted)

• Journal of Life Science
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• v.14 no.5
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• pp.800-808
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• 2004

Resveratrol, a phytoalexin found at high levels in grapes and in grape products such as red wine, has been reported to possess a wide range of biological and pharmacological activities including antioxident, anti-inflammatory, anti-mutagenic, and anti-carcinogenic effects. According to recent studies, this compound is an effective inhibitor of cell growth in general, triggers partial arrest of the cell cycle and induce apoptosis. In this study, the anti-proliferative effects of resveratrol in A549 human lung carcinoma cells were investigated. It is shown that resveratrol induced the growth inhibition in a time-dependent manner and morphological changes of A549 cells, which were associated with induction of S phase arrest of the cell cycle and apoptotic cell death. The Bcl-$X_L$levels were markedly down-regulated in resveratrol treated cells, however, Bax and Bcl-2 were remained unchanged. Resveratrol treatment induced the proteolytic degradation of Sp-l and proliferating cell nuclear antigen protein, and inhibited the expression of $\beta$-catenin protein. Resveratrol treatment also induced a marked up-regulation of cyclin-dependent kinase (Cdk) inhibitor p21 and inhibited the kinase activities of Cdk2 and Cdk4. In addition, resveratrol treatment inhibited the levels of cyclooxygenase (COX)-2 mRNA and protein, and the release of prostagladin E2 without alteration of COX-1 expression. Taken together, these findings suggest that resveratrol may be a potential chemotherapeutic agent for the control of human lung carcinorma cells.

• Natural Product Sciences
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• v.4 no.4
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• pp.263-267
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• 1998

From the dried flower-buds of Syzygium aromaticum Merr. et Perry (Myrtaceae), seven compounds, i.e., eugenol (1), oleanolic acid (2), kaempferol 7-O-metylether (3), 3,3',4-tri-O-methylellagic acid (4), maslinic acid (5), ${\beta}-sitosterol-3-O-glucoside$ (6), and isorhamnetin 3-O-glucoside (7) were isolated. Compound 1 showed cyclooxygenase-2 (COX-2) inhibitory activity.

• Clinical and Experimental Pediatrics
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• v.60 no.6
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• pp.175-180
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• 2017

Purpose: Plasma level of B-type natriuretic peptide (BNP), an emerging, sensitive, and specific biomarker of hemodynamically significant patent ductus arteriosus (PDA), rapidly decreases in infants receiving cyclooxygenase inhibitors for ductal closure. We investigated the usefulness of serial BNP measurement as a guide for individual identification of early constrictive responses to ibuprofen in preterm infants with symptomatic PDA (sPDA). Methods: Before March 2010, the standard course of pharmacological treatment was initiated with indomethacin (or ibuprofen) and routinely followed by 2 additional doses at intervals of 24 hours. After April 2010, individualized pharmacological treatment was used, starting with the first dose of ibuprofen and withholding additional ibuprofen doses if the BNP concentration was <600 pg/mL and clinical symptoms of PDA improved. Results: The BNP-guided group received significantly fewer doses of ibuprofen than the standard group did during the first course of treatment and the entire study period. The need for further doses of cyclooxygenase inhibitors and for surgical ligation was not significantly different between the 2 groups. No significant differences were seen in clinical outcomes and/or complications related to sPDA and/or pharmacological treatment. Conclusion: Individualized BNP-guided pharmacological treatment may be used clinically to avoid unnecessary doses of cyclooxygenase inhibitors without increasing the ductal closure failure and the short-term morbidity related to sPDA.

• Toxicological Research
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• v.35 no.1
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• pp.83-91
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• 2019

Nanoparticles (NPs) have been recognized as both useful tools and potentially toxic materials in various industrial and medicinal fields. Previously, we found that zinc oxide (ZnO) NPs that are neurotoxic to human dopaminergic neuroblastoma SH-SY5Y cells are mediated by lipoxygenase (LOX), not cyclooxygenase-2 (COX-2). Here, we examined whether human bone marrow-derived mesenchymal stem cells (MSCs), which are different from neuroblastoma cells, might exhibit COX-2- and/or LOX-dependent cytotoxicity of ZnO NPs. Additionally, changes in annexin V expression, caspase-3/7 activity, and mitochondrial membrane potential (MMP) induced by ZnO NPs and ZnO were compared at 12 hr and 24 hr after exposure using flow cytometry. Cytotoxicity was measured based on lactate dehydrogenase activity and confirmed by trypan blue staining. Rescue studies were executed using zinc or iron chelators. ZnO NPs and ZnO showed similar dose-dependent and significant cytotoxic effects at concentrations ${\geq}15{\mu}g/mL$, in accordance with annexin V expression, caspase-3/7 activity, and MMP results. Human MSCs exhibited both COX-2 and LOX-mediated cytotoxicity after exposure to ZnO NPs, which was different from human neuroblastoma cells. Zinc and iron chelators significantly attenuated ZnO NPs-induced toxicity. Conclusively, these results suggest that ZnO NPs exhibit both COX-2- and LOX-mediated apoptosis by the participation of mitochondrial dysfunction in human MSC cultures.

• Journal of Microbiology and Biotechnology
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• v.25 no.10
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• pp.1697-1701
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• 2015

The anticancer and anti-inflammatory activities of probiotic Lactococcus lactis NK34 were demonstrated. Treatment of cancer cells such as SK-MES-1, DLD-1, HT-29, LoVo, AGS, and MCF-7 cells with 10⁶ CFU/well of L. lactis NK34 resulted in strong inhibition of proliferation (>77% cytotoxicity, p < 0.05). The anti-inflammatory activity of L. lactis NK34 was also demonstrated in lipopolysaccharide-induced RAW 264.7 cells, where the production of nitric oxide and proinflammatory cytokines (tumor necrosis factor-α, interleukin-18, and cyclooxygenase-2) was reduced. These results suggest that L. lactis NK34 could be used as a probiotic microorganism to inhibit the proliferation of cancer cells and production of proinflammatory cytokines.

• Proceedings of the Korean Society of Toxicology Conference
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• 2001.05a
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• pp.152-152
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• 2001

Curcumin, a yellow coloring ingredient of turmeric (Curcuma longa L., Zingiberaceae), has been shown to inhibit experimental carcinogenesis and mutagenesis, but molecular mechanisms underlying its chemopreventive activities remain unclear.(omitted)

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.147.3-148
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• 2003

Recently, there have been considerable efforts to search for naturally occurring substances for the intervention of carcinogenesis. Curcumin, a yellow coloring ingredient of turmeric (Curcuma longa L., Zingiberaceae), has been shown to inhibit experimental carcinogenesis and mutagenesis, but molecular mechanisms underlying its chemopreventive activities remain unclear. In the present work, we found that curcumin inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced expression of CPX-2 in female ICR mouse skin when applied topically 30 min prior to TPA as determined by both immunoblot and immunohistochemical analyses. (omitted)

• Journal of Applied Biological Chemistry
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• v.66
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• pp.39-45
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• 2023

Biorenovation is a biotransformation method that converts the structure of chemical compounds and natural product through biocatalytic metabolism of microorganism and could enhance biological effectiveness and mitigate cytotoxicity compared to its substrates. Althaea rosea L. has been used as oriental medicine and is known for physiological efficacies such as antiurolithiatic, anti-inflammatory, and anti-cancer activities. A. rosea L. callus, the plant tissue grown to protect its wound, has been reported to have antioxidant and whitening effects. However, mechanisms of its other activity such as inflammation have not yet been investigated. In this study, we extracted A. rosea L. callus (AR) and produced biorenovated AR (ARBR), and then analyzed anti-inflammatory effect in Lipopolysaccharide-induced RAW 264.7 macrophage at 50, 100, 200 ㎍/mL of ARBR. As a result of inhibition test of nitric oxide production, it was found that ARBR was superior to AR without apparent toxicity. Furthermore, ARBR significantly inhibited production of prostaglandin E₂, inducible nitric oxide synthase, cyclooxygenase-2 and pro-inflammatory cytokines including Tumor necrosis factor-α, Interleukin-6, Interleukin-1β in a concentration-dependent manner. In conclusion, we suggest that ARBR could regulate the excessive inflammatory response to an appropriate level and be a promising material for functional cosmetics and pharmaceuticals.

• BMB Reports
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• v.45 no.2
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• pp.108-113
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• 2012

Protopine is an isoquinoline alkaloid contained in plants in northeast Asia. In this study, we investigated whether protopine derived from Hypecoum erectum L could suppress lipopolysaccharide (LPS)-induced inflammatory responses in murine macrophages (Raw 264.7 cells). Protopine was found to reduce nitric oxide (NO), cyclooxygenase-2 (COX-2), and prostaglandin $E_2$ ($PGE_2$) production by LPS-stimulated Raw 264.7 cells, without a cytotoxic effect. Pre-treatment of Raw 264.7 cells with protopine reduced the production of pro-inflammatory cytokines. These inhibitory effects were caused by blocking phosphorylation of mitogen-activated protein kinases (MAP kinases) and also blocking activation of a nuclear factor kappa-light-chain-enhancer of activated B cells (NF-${\kappa}B$).