• Biomolecules & Therapeutics
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• v.29 no.3
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• pp.331-341
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• 2021

Liver cancer is a common tumor and currently the second leading cause of cancer-related mortality globally. Liver cancer is highly related to inflammation as more than 90% of liver cancer arises in the context of hepatic inflammation, such as hepatitis B virus and hepatitis C virus infection. Despite significant improvements in the therapeutic modalities for liver cancer, patient prognosis is not satisfactory due to the limited efficacy of current drug therapies in anti-metastatic activity. Therefore, developing new effective anti-cancer agents with anti-metastatic activity is important for the treatment of liver cancer. In this study, SP-8356, a verbenone derivative with anti-inflammatory activity, was investigated for its effect on the growth and migration of liver cancer cells. Our findings demonstrated that SP-8356 inhibits the proliferation of liver cancer cells by inducing apoptosis and suppressing the mobility and invasion ability of liver cancer cells. Functional studies revealed that SP-8356 inhibits the mitogen-activated protein kinase and nuclear factor-kappa B signaling pathways, which are related to cell proliferation and metastasis, resulting in the downregulation of metastasis-related genes. Moreover, using an orthotopic liver cancer model, tumor growth was significantly decreased following treatment with SP-8356. Thus, this study suggests that SP-8356 may be a potential agent for the treatment of liver cancer with multimodal regulation.

• Journal of Life Science
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• v.31 no.8
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• pp.736-744
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• 2021

Artemisia princeps Pampanini is an herbal medicine widely used to immune function-related diseases, such as anti-oxidative, anti-inflammatory, and antibacterial agents. In this study, we investigated the anti-inflammatory effects of AP extract and underlying mechanisms were evaluated in RAW 264.7 cells. The effects of AP extract were also studied in a complete Freund's adjuvant (CFA)-induced arthritis and lipopolysaccharide (LPS)-induced inflammation mouse model. In RAW 264.7 cells, AP extracts significantly inhibited the LPS-induced nitric oxide (NO) production and inducible NO synthase and cyclooxygenase-2 protein expression. The LPS-induced phosphorylation of mitogen-activated protein kinases and nuclear factor-κB was also significantly blocked by AP extract in RAW 264.7 cells. Oral administration of AP extract suppressed the increase in mouse paw edema and spleen index compared to CFA-treated mice group. Histologically, the infiltration of inflammatory cells was increased in cartilage and synovium in the CFA-treated mouse group, whereas it was suppressed in the AP extract-administered group. Furthermore, AP extract treatment significantly reduced the inflammatory cytokine, tumor necrosis factor-α, levels in CFA and LPS-treated mouse. In conclusion, the anti-inflammatory and anti-arthritis effect of AP extract was confirmed in both in vitro and in vivo models, suggesting that Artemisia princeps Pampanini may be a candidate material for arthritis treatment.

• IMMUNE NETWORK
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• v.15 no.2
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• pp.58-65
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• 2015

Melanoma is the most aggressive skin cancer and its incidence is gradually increasing worldwide. Patients with metastatic melanoma have a very poor prognosis (estimated 5-year survival rate of <16%). In the last few years, several drugs have been approved for malignant melanoma, such as tyrosine kinase inhibitors and immune checkpoint blockades. Although new therapeutic agents have improved progression-free and overall survival, their use is limited by drug resistance and drug-related toxicity. At the same time, adoptive cell therapy of metastatic melanoma with tumor-infiltrating lymphocytes has shown promising results in preclinical and clinical studies. In this review, we summarize the currently available drugs for treatment of malignant melanoma. In addition, we suggest cytokine-induced killer (CIK) cells as another candidate approach for adoptive cell therapy of melanoma. Our preclinical study and several previous studies have shown that CIK cells have potent anti-tumor activity against melanomas in vitro and in an in vivo human tumor xenograft model without any toxicity.

• Korean Journal of Food Science and Technology
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• v.49 no.6
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• pp.710-713
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• 2017

This study evaluates the ability of corn silk (Zea mays L.) extract to function as a natural anti-inflammatory and anti-atopic therapeutic agent. The anti-inflammatory effects of corn silk were evaluated by measuring the inhibitory activities of nitric oxide (NO) and production of tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$. Anti-atopic effects were assessed by measuring the repression of thymus and activation-regulated chemokine (TARC). These results indicated that NICS-1 (corn silk ethanol extract) and NICS-3 (high maysin corn silk ethanol extract) functioned as anti-inflammatory agents by down-regulating LPS-induced NO and TNF-${\alpha}$. Additionally, two extracts showed weak repression of TARC expression levels in tumor necrosis factor TNF-${\alpha}$ plus IFN-${\gamma}$ induced HaCaT cells, respectively. These results suggest that corn silk extracts have anti-inflammatory and anti-atopic activities, and thus have the potential to reduce and alleviate the symptoms associated with atopic dermatitis.

• Journal of Hospice and Palliative Care
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• v.19 no.4
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• pp.331-334
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• 2016

Purpose: Advanced cancer may accompany cold sweat as paraneoplastic symptom. Few studies have been performed on the efficacy of non-steroid anti-inflammatory drug (NSAID) in advanced cancer patients who sweated without fever. Methods: To select study participants, medical records were retrospectively reviewed for patients who satisfied the following criteria: 1) incurable, advanced solid cancer; 2) Cold sweating of 4 or higher on the numeric rating scale (NRS) 4; 3) No evidence of infection or hypoglycemia; 4) No newly started opioid or anti-hormonal agents within one month; 5) NSAID prescription for the management of cold sweating and 6) Documented NRS information before and after NSAID administration. Results: A total of 13 patients were selected after excluding four patients due to lack of NRS information or fever. The mean age was 59 years old (range: 50~71), and nine patients (69%) were male. Bile duct cancer was the most common primary tumor followed by pancreatic cancer, gastric cancer and prostate cancer. The mean NRS of cold sweating dropped from baseline 6.5 (min-max: 4~10) to 1.9 at the follow-up assessment (min-max: 0~5). The mean follow-up period was 9.1 days (range: 2~30 days) from NSAID treatment to assessment. Conclusion: NSAID was effective medication for management of sweating without fever in patients with advanced cancer.

• Biomedical Science Letters
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• v.17 no.3
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• pp.225-230
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• 2011

Indirubin is the active ingredient of Danggui Longhui Wan, a mixture of plants that is used in traditional Chinese medicine to treat chronic diseases. In this study we investigated the anti-inflammatory effects of an indirubin derivative, indirubin-3’-monoxime-5-sulphonic acid (I3M-5S, $C_{16}H_{11}N_3O_5S$). We found that I3M-5S inhibits the production of various inflammatory mediators such as nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$) as well as inflammatory cytokines, tumor necrosis factor-${\alpha}$ and interleukin-6 in lipopolysaccharide (LPS) stimulated murine macrophage, RAW264.7 cells. In addition, the expression of inducible nitric oxide synthase and cyclooxygenase-2, which are essential enzymes to produce NO and $PGE_2$, respectively, was blocked by I3M-5S treatment in LPS-stimulated RAW264.7 cells. Present data suggest that I3M-5S exhibits potent anti-inflammatory activity in cultured macrophages and merit further study as potential therapeutic agents for inflammatory disorders.

• Biomolecules & Therapeutics
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• v.22 no.4
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• pp.334-340
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• 2014

In this study, 23 oleanane-type triterpenoid saponins were isolated from a methanol extract of the roots of Pulsatilla koreana. The NF-${\kappa}B$ inhibitory activity of the isolated compounds was measured in $TNF{\alpha}$-treated HepG2 cells using a luciferase reporter system. Compounds 19-23 inhibited $TNF{\alpha}$-stimulated NF-${\kappa}B$ activation in a dose-dependent manner, with $IC_{50}$ values ranging from $0.75-8.30{\mu}M$. Compounds 19 and 20 also inhibited the $TNF{\alpha}$-induced expression of iNOS and ICAM-1 mRNA. Moreover, effect of the isolated compounds on PPARs transcriptional activity was assessed. Compounds 7-11 and 19-23 activated PPARs the transcriptional activity significantly in a dose-dependent manner, with $EC_{50}$ values ranging from $0.9-10.8{\mu}M$. These results suggest the presence of potent anti-inflammatory components in P. koreana, and will facilitate the development of novel anti-inflammatory agents.

• 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 Marine Bioscience and Biotechnology
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• v.2 no.2
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• pp.86-93
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• 2007

Chronic inflammation has been known to have a close relationship with several diseases including periodontitis, colitis, hepatitis and arthritis. Recently anti-inflammatory agents have been developed from marine natural resources. In this study, Ecklonia cava (EC) was found to have anti-inflammatory effect. Ethanolic extract of EC belonging to brown algae exhibited an excellent inhibitory effect on the production of inflammatory mediators such as tumor necrosis factor-${\alpha}$, interleukin-$1{\beta}$, interleukin-6 and prostaglandin $E_2$ by RA W264.7 cells. Furthermore, in reporter gene assay and western blot analysis, EC extract exerted anti-inflammatory effect via inactivation of NF-${\kappa}B$ transcription factor that regulates the expression of these inflammatory mediators in macrophages. In addition, EC extract inhibited the activity of matrix metalloproteinase that play an important role in chronic inflammation. These results suggest that EC extract may provide a pharmaceutical potential in inhibiting chronic inflammation.

• Molecules and Cells
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• v.42 no.11
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• pp.755-762
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• 2019

Despite decades of research into colorectal cancer (CRC), there is an ongoing need for treatments that are more effective and safer than those currently available. Lactic acid bacteria (LAB) show beneficial effects in the context of several diseases, including CRC, and are generally regarded as safe. Here, we isolated a Lactobacillus rhamnosus (LR)-derived therapeutic protein, p8, which suppressed CRC proliferation. We found that p8 translocated specifically to the cytosol of DLD-1 cells. Moreover, p8 down-regulated expression of Cyclin B1 and Cdk1, both of which are required for cell cycle progression. We confirmed that p8 exerted strong anti-proliferative activity in a mouse CRC xenograft model. Intraperitoneal injection of recombinant p8 (r-p8) led to a significant reduction (up to 59%) in tumor mass when compared with controls. In recent years, bacterial drug delivery systems (DDSs) have proven to be effective therapeutic agents for acute colitis. Therefore, we aimed to use such systems, particularly LAB, to generate the valuable therapeutic proteins to treat CRC. To this end, we developed a gene expression cassette capable of inducing secretion of large amounts of p8 protein from Pediococcus pentosaceus SL4 (PP). We then confirmed that this protein (PP-p8) exerted anti-proliferative activity in a mouse CRC xenograft model. Oral administration of PP-p8 DDS led to a marked reduction in tumor mass (up to 64%) compared with controls. The PP-p8 DDS using LAB described herein has advantages over other therapeutics; these advantages include improved safety (the protein is a probiotic), cost-free purification, and specific targeting of CRC cells.