• Journal of Microbiology and Biotechnology
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• v.17 no.9
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• pp.1546-1549
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• 2007

Chitosan oligosaccharide (COS, 3 kDa

• Fisheries and Aquatic Sciences
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• v.15 no.1
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• pp.29-36
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• 2012

Osteosarcoma is the most common primary malignancy of bone, and patients often develop pulmonary metastasis. The mechanisms underlying osteosarcoma metastasis remain to be elucidated. Recently, anti-inflammatory agents were shown to be useful in the treatment of tumor progression. We previously isolated a natural anti-inflammatory peptide from the seahorse Hippocampus kuda bleeler. Here, we examined the antitumor metastatic activity of this peptide and investigated its mechanism. The peptide significantly inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced invasive migration of human osteosarcoma MG-63 cells. Its inhibitory effect on invasive migration was associated with reduced expression of matrix metalloproteinases (MMP1 and MMP2). In addition, TPA stimulation increased intracellular reactive oxygen species (ROS) generation and small GTPase Rac1 expression, whereas the peptide decreased ROS generation and Rac1 activation. Taken together, these results suggest that the peptide inhibits invasive migration of MG-63 osteosarcoma cells by inhibiting MMP1 and MMP2 expression through downregulation of Rac1-ROS signaling.

• Journal of Physiology & Pathology in Korean Medicine
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• v.28 no.5
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• pp.494-498
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• 2014

It is well known that Desomodii Herba (DH) has an effect to eliminate dampness, relieve jaundice and to clear away toxic material, relieve swelling in Korean Medicine. However, the effect of DH on breast cancer invasion is unknown. In this study, we investigated the inhibitory effect of DH extracts (DHE) on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced matrix metalloproteinase-9 (MMP-9) expression and cell invasion, as well as the molecular mechanisms involved in MCF-7, human breast cancer cells. DHE inhibits TPA-induced MMP-9 protein and mRNA expressions in a dose-dependent fashion. DHE also inhibited the TPA-induced transcriptional activation of nuclear factor-kappa B (NF-${\kappa}B$). These results indicate that DHE-mediated inhibition of TPA-induced MMP-9 expression and cell invasion involves the suppression of NF-${\kappa}B$ pathway in MCF-7 cells.

• BMB Reports
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• v.47 no.5
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• pp.262-267
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• 2014

Bcl-2 interacting cell death suppressor (Bis) has been shown to have anti-apoptotic and anti-stress functions. Recently, increased Bis expression was reported to correlate with glioma aggressiveness. Here, we investigated the effect of Bis knockdown on the acquisition of the invasive phenotype of A172 glioma cells, induced by 12-O-Tetradecanoylphorbol-3-acetate (TPA), using a Transwell assay. Bis knockdown resulted in a significant decrease in the migration and invasion of A172 cells. Furthermore, Bis knockdown notably decreased TPA-induced matrix metalloproteinase-9 (MMP-9) activity and mRNA expression, as measured by zymography and quantitative real time PCR, respectively. A luciferase reporter assay indicated that Bis suppression significantly down-regulated NF-${\kappa}B$-driven transcription. Finally, we demonstrated that the rapid phosphorylation and subsequent degradation of $I{\kappa}B-{\alpha}$ induced by TPA was remarkably delayed by Bis knockdown. These results suggest that Bis regulates the invasive ability of glioma cells elicited by TPA, by modulating NF-${\kappa}B$ activation, and subsequent induction of MMP-9 mRNA.

• BMB Reports
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• v.52 no.12
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• pp.695-699
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• 2019

Cytokine-induced apoptosis inhibitor 1 (CIAPIN1), known as an anti-apoptotic and signal-transduction protein, plays a pivotal role in a variety of biological processes. However, the role of CIAPIN1 in inflammation is unclear. We investigated the protective effects of CIAPIN1 in lipopolysaccharide (LPS)-exposed Raw 264.7 cells and against inflammatory damage induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in a mouse model using cell-permeable Tat-CIAPIN1. Transduced Tat-CIAPIN1 significantly reduced ROS production and DNA fragmentation in LPS-exposed Raw 264.7 cells. Also, Tat-CIAPIN1 inhibited MAPKs and NF-κB activation, reduced the expression of Bax, and cleaved caspase-3, COX-2, iNOS, IL-6, and TNF-α in LPS-exposed cells. In a TPA-induced animal model, transduced Tat-CIAPIN1 drastically decreased inflammation damage and inhibited COX-2, iNOS, IL-6, and TNF-α expression. Therefore, these findings suggest that Tat-CIAPIN1 might lead to a new strategy for the treatment of inflammatory skin disorders.

• Biomolecules & Therapeutics
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• v.31 no.6
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• pp.682-691
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• 2023

Cell transformation induced by epidermal growth factor (EGF) and 12-O-tetradecanoylphorbol-13-acetate (TPA) is a critical event in cancer initiation and progression, and understanding the underlying mechanisms is essential for the development of new therapeutic strategies. Licorice extract contains various bioactive compounds, which have been reported to have anticancer and anti-inflammatory effects. This study investigated the cancer preventive efficacy of licochalcone D (LicoD), a chalcone derivative in licorice extract, in EGF and TPA-induced transformed skin keratinocyte cells. LicoD effectively suppressed EGF-induced cell proliferation and anchorage-independent colony growth. EGF and TPA promoted the S phase of cell cycle, while LicoD treatment caused G1 phase arrest and down-regulated cyclin D1 and up-regulated p21 expression associated with the G1 phase. LicoD also induced apoptosis and increased apoptosis-related proteins such as cleaved-caspase-3, cleaved-caspase-7, and Bax (Bcl2-associated X protein). We further investigated the effect of LicoD on the AKT signaling pathway involved in various cellular processes and found decreased p-AKT, p-GSK3β, and p-NFκB expression. Treatment with MK-2206, an AKT pharmacological inhibitor, suppressed EGF-induced cell proliferation and transformed colony growth. In conclusion, this study demonstrated the potential of LicoD as a preventive agent for skin carcinogenesis.

• Preventive Nutrition and Food Science
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• v.16 no.4
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• pp.283-290
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• 2011

The recent increase of colon, breast, and prostate cancer incidence in Korea has been attributed to a diet pattern change to a more Western style, in which the foods eaten are higher in protein and fat. Whether high protein intake itself stimulates tumor cell growth and exacerbates disease status has been investigated, however, many epidemiological studies have inconsistent results between meat intake and the risk of certain cancers. These inconsistent results are partly because of the difficulty of studying the effects of just the meat intake. Other factors, such as overall meal context, could not be completely excluded in the study. To address the question of whether high protein itself is independently associated with carcinogenesis, we initiated ICR mice with 200 nmol ($50{\mu}g$) 7,12-dimethylbenz[a]anthracene (DMBA) and fed animals either a normal diet (ND, 14% casein) or a high protein diet (HPD, 50% casein) for 15 weeks with 12-O-tetradecanoylphorbol-13-acetate (TPA) promotion in two-stage skin carcinogenesis protocol. There was no significant difference between ND and HPD group in food intake and body weight throughout the experiment. However, tumor multiplicity of the HPD group was decreased by 75.5% compared to that of the ND group. In addition, HPD inhibited skin hyperplasia and epidermal cell proliferation. Western analyses with whole skin lysates showed that HPD inhibited TPA-induced Akt (S473), S6K (T389), 4E-BP1 (Thr 37/46) and Erk1/2 (Thr202/Tyr204) phosphorylation as well as COX-2 expression. Taken together, these data suggest that a high protein diet has an anticarcinogenic effect by inhibiting the TPA-induced Akt signaling pathway.

• Journal of Ginseng Research
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• v.44 no.2
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• pp.274-281
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• 2020

Background: Ultraviolet (UV) goes through the epidermis and promotes release of inflammatory cytokines in keratinocytes. Granulocyte-macrophage colony-stimulating factor (GM-CSF), one of the keratinocyte-derived cytokines, regulates proliferation and differentiation of melanocytes. Extracellular signal-regulated kinase (ERK1/2) and protein kinase C (PKC) signaling pathways regulate expression of GM-CSF. Based on these results, we found that ginsenoside Rh3 prevented GM-CSF production and release in UV-B-exposed SP-1 keratinocytes and that this inhibitory effect resulted from the reduction of PKCδ and ERK phosphorylation. Methods: We investigated the mechanism by which ginsenoside Rh3 from Panax ginseng inhibited GM-CSF release from UV-B-irradiated keratinocytes. Results: Treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA) or UV-B induced release of GM-CSF in the SP-1 keratinocytes. To elucidate whether the change in GM-CSF expression could be related to PKC signaling, the cells were pretreated with H7, an inhibitor of PKC, and irradiated with UV-B. GM-CSF was decreased by H7 in a dose-dependent manner. When we analyzed which ginsenosides repressed GM-CSF expression among 15 ginsenosides, ginsenoside Rh3 showed the largest decline to 40% of GM-CSF expression in enzyme-linked immunosorbent assay. Western blot analysis showed that TPA enhanced the phosphorylation of PKCδ and ERK in the keratinocytes. When we examined the effect of ginsenoside Rh3, we identified that ginsenoside Rh3 inhibited the TPA-induced phosphorylation levels of PKCδ and ERK. Conclusion: In summary, we found that ginsenoside Rh3 impeded UV-B-induced GM-CSF production through repression of PKCδ and ERK phosphorylation in SP-1 keratinocytes.

• Toxicological Research
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• v.26 no.1
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• pp.29-35
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• 2010

The present study was conducted to investigate the antimutagenic potential of the methanolic extract from the leaves of sweet potato (Ipomea batatas, IB) with the SOS chromotest (umu test) and Salmonella typhimurium TA 98 and TA 100. The anticarcinogenic effects were also studied by calculation of the $IC_{50}$ on human cancer cell lines and investigating the function of gap junction in rat liver epithelial cells. The IB extract inhibited dose-dependently the ${\beta}$-galactosidase activity induced spontaneously at concentration of more than 200 mg/ml in S. typhimurium TA 1535/pSK 1002, and decreased significantly (p < 0.01) the ${\beta}$-galactosidase activities induced by mutagen 6-chloro-9-[3-(2-chloroethylamino)proylamino]-2-methoxyacridine dihydrochloride (ICR) at dose of more than 0.4 mg/0.1 ml. The IB extract showed no effect on the spontaneous reversions of S. typhimurium TA 98 and 100 but benzo(${\alpha}$)pyrene (BaP)-stimulated reversions were decreased dose-dependently (p < 0.01) at the concentration of more than 100 mg/ml. The $IC_{50}$ value of stomach cancer cells was lower than that of normal rat liver epithelial cells, but the values of colon and uterine cancer cell lines were similar to those of normal rat liver epithelial cells. The transfer of dye through gap junctions was not affected by treatment of the IB extracts at any concentration during treatment periods. The simultaneously treatment of IB extract and 12-O-tetradecanoylphorbol-13-acetate (TPA) effectively prevented the inhibition of dye transfer induced by TPA 1 hour after treatment at all exposed concentrations. The number of gap junctions was significantly (p < 0.01) increased by the treatment with IB extract at concentrations of more than 40 ${\mu}g$/ml. The inhibition of the expression of gap junction proteins by TPA (0.01 ${\mu}g$/ml) was recovered dose dependently by the simultaneous treatment of IB extracts. Our data suggest that Ipomea batatas has antimutagenic and anticarcionogenic activity in vitro.

• Journal of People, Plants, and Environment
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• v.24 no.1
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• pp.53-62
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• 2021

Background and objective: Dermatitis is a chronic disease accompanied by such symptoms as itching and dry skin. The environment and diet can aggravate dermatitis, so attention to skin care is essential. Colocasia esculenta is used in various manners and for different purposes, including with regard to inflammation, aging, and the digestive system. The anti-inflammatory effect of Colocasia esculenta water extract was confirmed using RAW 264.7 macrophages with regard to male ICR mice. Methods: In the case of the ICR mice, 5% 12-O-Tetradecanoylphorbol-13-acetate (TPA) was used to cause inflammation for 7 days, and 100 μL of Colocasia esculenta water extract and panthenol were administered orally for 10 days. In addition, RT-PCR, NO, ELISA was conducted. Results: As a result of reverse transcription polymerase chain reaction (RT-PCR) using RAW 264.7 macrophages stimulated with lipopolysaccharide (LPS), it was found that Colocasia esculenta water extract reduced the expression of inflammatory cytokines. As a result of hematoxylin and eosin (H&E) staining using mouse ear tissue, Colocasia esculenta water extract reduced ear thickness and showed an effect of suppressing ear edema. In addition, compared to the TPA-treated group, the Colocasia esculenta extract-treated group had reduced nitric oxide (NO) production by 18.23 μM and IL-13 production decreased by 136.55 pg/ml. Conclusion: Colocasia esculenta water extract has been shown to be effective in lowering inflammatory cytokine production. These results suggest that Colocasia esculenta water extracts can be used as natural products to treat dermatitis.