• Journal of the Korean Society of Food Science and Nutrition
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• v.44 no.2
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• pp.200-207
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• 2015

Various natural products or their derivatives, mostly originating from plants, fungi, and bacteria, have been exploited as therapeutic drugs to treat various human diseases. In addition to previously explored organisms, research on natural compounds has now expanded into unexamined living organisms in order to identify novel bioactive substances. Here, we determined whether or not the larval form of the mealworm beetle Tenebrio molitor, a species of darkling beetle, contains cytotoxic substances that exclusively affect cancer cell viability. Ethanol extract and its solvent partitioned fractions, hexane and ethyl acetate fractions, showed anticancer effects against various human cancer cells derived from the prostate (PC3 and 22Rv1), cervix (HeLa), liver (PLC/PRF5, HepG2, Hep3B, and SK-HEP-1), colon (HCT116), lung (NCI-H460), breast (MDA-MB231), and ovary (SKOV3). Cell death induced by the fractions was a mix of apoptosis, necrosis, and autophagy. The hexane fraction was administered intraperitoneally to nude mice bearing a hepatocellular carcinoma SK-HEP-1 and showed inhibition of tumor growth in vivo. Therefore, we concluded that worm extracts contain cytotoxic substances, which can be enriched by proper fractionation protocols, and further separation and purification could lead to the identification of novel molecules to treat human cancers.

• Tuberculosis and Respiratory Diseases
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• v.46 no.2
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• pp.229-240
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• 1999

Background: The impact of the immune response on cancer gene therapy using viral vectors to deliver a "suicide gene" is currently unclear. A vigrous immune response targeted at viral proteins or transgene may enhance the efficacy of tumor destruction and even augment responses to tumor antigens. These responses may involve the release of cytokines and stimulation of tumor specific cytotoxic T-lymphocytes that enhance therapeutic efficacy. On the other hand, a vigorous rapid cellular immune response may destroy cells expressing the therapeutic gene and attenuate the response to therapy. Furthermore, development of neutralizing antibody responses may prevent readministration of virus, a potentially significant limitation. Evaluating the significance of these limitations in animal models and developing solutions are therefore of obvious importance. Methods: After retroviral transduction of mouse mesothelioma cell line(AB12) with Herpes Simplex Virus thymidine kinase (HSVtk) gene in vitro, subcutaneous flank tumors were established. To study the effect of intact immune system on efficacy of tumor erradication, the ability of the HSVtk/ganciclovir system to inhibit tumor growth was compared among normal Balb/c mice, immunodeficient Balb/c-nude and SCID mice, and Balb/c mice immunosuppressed with cyclosporin. Results: Ganciclovir treatment resulted in greater inhibition of tumor growth in Balb/c mice compared with immunodeficient Balb/c-nude mice and SCID mice(in immunodeficient mice, there were no growth inhibition by ganciclovir treatment). Ganciclovir treatment resulted in greater inhibition of tumor growth in noncyclosporin (CSA) treated Balb/c mice compared with CSA treated Balb/c mice. On day 8, mean ganciclovir-treated tumor volume were 65% of control tumor volume in Balb/c mice versus 77% control tumor volume in CSA-treated Balb/c mice. This effect was still evident during therapy (day 11 and 13). On day 13, non-CSA treated tumor volume was 35% of control tumor volume versus 60% of control tumor volume in CSA treated Balb/c mice. Duration of expression of HSVtk was not affected by the immunosuppression with CSA. Conclusion: These results indicate that the immune responses against retrovirally transduced cells enhance the efficacy of the HSVtk/ganciclovir system. These findings have important implications for clinical trials using currently available retrovirus vectors as well as for future vector design.

• Korean Journal of Food Science and Technology
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• v.29 no.1
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• pp.161-166
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• 1997

Tissue thromboplastin (tissue factor), a membrane bound glycoprotein is an important initiating factor in blood coagulation cascade, which leads to the formation of thrombin by activating both factor X and IX. Activation of blood coagulation by TF is essential for blood injury, and stimulates the blood coagulation in myocardial infarction, cancer and blood coagulatory diseases. High density lipoprotein, apolipoprotein A-II were known to be biological TF inhibitors. Recently, studies on search for TF inhibitors from natural products have been active in Korea. Among the edible mushrooms screened for inhibitory activities on the TF, Lentinus edodes showed the most strong activity, followd by Agaricus bisporus and Ganoderma lucidium. And the fractionation of the above mushrooms with the chloroform ($CHCl_3$) and ethylacetate (EtOAc) was done and evaluated for the inhibitory activities on TF. In Ganoderma lucidium, $CHCl_3$ fraction and $H_2O$ layer were not active, but EtOAc fraction exhibited a strong inhibitory activity on TF and the $IC_{50}$ value was $1.07{\times}10^{-4}\;g$. In the case of Agaricus bisporus, there were no inhibitory activities on the TF in all of the fractions. $CHCl_3$ fraction and $H_2O$ layer of Lentinus edodes did not show inhibition on the TF but EtOAc fraction showed strong inhibition on the TF, and the $IC_{50}$ value was $7.70{\times}10^{-4}\;g$.

• Korean Journal of Environmental Biology
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• v.24 no.1 s.61
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• pp.46-52
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• 2006

The mercury is among the most highly bioconcentrated toxic trace metals. Many national and international agencies and organisations have targeted mercury for the possible emission control. The mercury toxicity depends on its chemical form, among which alkylmercury compounds are the most toxic. A human cervix uterus cancer cell line HeLa cells was employed to investigate the effect of the toxic heavy metal mercury (Hg) and ionizing radiation. In the in vitro comet assays for the genotoxicity in the HeLa cells, the group of Hg treatment after irradiation showed higher DNA breakage than the other groups. The tail extent moment and olive tail moment of the control group were $4.88{\pm}1.00\;and\;3.50{\pm}0.52$ while the values of the only Hg treatment group were $26.90{\pm}2.67\;and\;13.16{\pm}1.82$, respectively. The tail extent moment and olive tail moment of the only 0.001, 0.005, 0.01 Hg group were $12.24{\pm}1.82,\;8.20{\pm}2.15,\;20.30{\pm}1.30,\;12.26{\pm}0.52,\;40.65{\pm}2.94\;and \;20.38{\pm}1.49$, respectively. In the case of Hg treatment after irradiation, the tail extent moment and olive tail moment of the 0.001, 0.005, 0.01 Hg group were $56.50{\pm}3.93,\;32.69{\pm}2.48,\;62.03{\pm}5.14,\;31.56{\pm}1.97,\;72.73{\pm}3.70\;and \;39.44{\pm}3.23$, respectively. The results showed that Hg induced DNA single-strand breaks or alkali labile sites as assessed by the Comet assay. It is in good agreement with the reported results. The mercury inhibits the repair of DNA. The bacterial formamidopyrimidine-DNA glycosylase (Epg protein) recognizes and removes some oxidative DNA base modifications. Enzyme inactivation by Hg (II) may therefore be due either to interactions with rysteine residues outside the metal binding domain or to very high-affinity binding of Hg (II) which readily removes Zn (II) from the zinc finger.

• Journal of the Korean Society of Food Science and Nutrition
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• v.38 no.8
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• pp.996-1002
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• 2009

This study was carried out to improve quality and increase anticancer effect of baechu kimchi by changing various kinds of salt. The baechu cabbages were brined with purified salt (P), natural sea salt (NS), natural sea salt without bittern (NS-B) or baked (Guwun) salt (G) and mixed with other ingredients. Thereafter, the kimchis were fermented for 7 days at $15^{\circ}C$. The changes in pH and acidity of the P and G kimchis were slower than those of NS and NS-B kimchis. NS-B and G kimchis promoted the growth of Leuconostoc sp.; however, it inhibited the growth of Lactobacillus sp. when compared with P and NS brined kimchis. The sensory evaluation results indicated that NS-B and G kimchis were better than P and NS kimchi in taste, color and overall acceptability. Rheological property of texture (cutting strength) of NS-B and G brined kimchis was also much better. Anticancer effects of the kimchi juices and methanol extracts were investigated on AGS human gastric adenocarcinoma cells and HT-29 human colon carcinoma cells by MTT assay. NS-B and G kimchis significantly retarded the growth of both cancer cells compared to P and NS kimchis. From these results, kind of salt is very important when kimchi is prepared. It proved that removing bittern from natural sea salt is good ancient tradition when brining the cabbage. Using the baked salt is also a better method to improve the quality and anticancer effect of kimchi.

• The Korean Journal of Physiology and Pharmacology
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• v.16 no.3
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• pp.159-165
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• 2012

Squamous cell carcinoma (SCC) and adenocarcinoma (AC) are the major histological types of non-small cell lung carcinoma (NSCLC). Although both SCCs and ACs have been characterized histologically and clinically, the precise mechanisms underlying their migration and invasion are not yet known. Here, we address the involvement in NSCLC of the p21-associated kinase1 (Pak1)/LIM kinase1 (LIMK1)/cofilin pathway, which recently has been reported to play a critical role in tumor migration and invasion. The Pak1/LIMK1/cofilin pathway was evaluated in tumors from SCC (n=35) and AC (n=35) patients and in SCC- and AC-type cell lines by western blotting, immunohistochemistry, and in vitro migration and invasion assays. The levels of phosphorylated Pak1, LIMK1, and cofilin in lung tumor tissues from SCC patients were increased as compared to normal tissues. In addition, immunohistochemistry showed greater expression of phosphorylated cofilin in SCC tissues. Expression of phosphorylated Pak1 and LIMK1 proteins was also significantly higher in SCC-type cells than in AC-type cells. Moreover, migration and invasion assays revealed that a higher percentage of SCC type cells exhibited migration and invasion compared to AC type cells. Migration was also decreased in LIMK1 knockdown SK-MES-1 cells. These findings suggest that the activation of the Pak1/LIMK1/cofilin pathway could preferentially contribute to greater tumor migration and invasion in SCC, relative to that in AC.

• The Korea Journal of Herbology
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• v.32 no.5
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• pp.27-38
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• 2017

Objective : In the present study, we examined whether Canavalia gladiata D.C. (CG) and Arctium lappa L., Redix (AL) mixture (CGAL), their components, lupeol and chicoric acid, regulate immune system and suppress the tumor in vitro and in vivo. Methods : LPS-induced reactive oxygen species (ROS) and nitric oxide (NO) were measured after treatment with CG extract (CGE), CGAL, lupeol, chicoric acid and lupeol and chicoric acid mixture (lupeol+CA) in Raw264.7 cell. To determine the effect of CGE on immune responses, immune cell population and IgG production were assessed in mice. To investigate the effect of CGAL and their component on anti-tumor activity, tumor volume and weight were measured, cell cycles and immune cell population were analyzed in MC38 injected tumor bearing mice. Also, NK cell activity was determined in splenocyte isolated from tumor bearing mice. Results : CGE, CGAL, lupeol, chicoric acid and lupeol+CA decreased the LPS-induced ROS and NO production without cell toxicity in RAW264.7 cells. CGE increased the immune cell populations of $CD4^+T$, $CD8^+T$ and macrophages in various immune organ of mice. In tumor bearing mice, CGAL, lupeol, chicoric acid and lupeol+CA suppressed tumor volume and weight. In cell cycle analysis, they decreased the percentages of S phase. In addition, CGAL, lupeol, chicoric acid and lupeol+CA immune cell populations of $CD4^+T$, $CD8^+Tcell$, NK cell and macrophage in tumor as well as NK cell activity. Conclusion : CGAL and its compounds may enhance immune responses and suppress tumor growth, and may be capable of developing health functional foods.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.5
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• pp.519-529
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• 2017

Sodium butyrate (SB) has various metabolic actions. However, its effect on dipeptidyl peptidase 4 (DPP-4) needs to be studied further. We aimed to evaluate the metabolic actions of SB, considering its physiologically relevant concentration. We evaluated the effect of SB on regulation of DPP-4 and its other metabolic actions, both in vitro (HepG2 cells and mouse mesangial cells) and in vivo (high fat diet [HFD]-induced obese mice). Ten-week HFD-induced obese C57BL/6J mice were subjected to SB treatment by adding SB to HFD which was maintained for an additional 16 weeks. In HepG2 cells, SB suppressed DPP-4 activity and expression at sub-molar concentrations, whereas it increased DPP-4 activity at a concentration of $1,000{\mu}M$. In HFD-induced obese mice, SB decreased blood glucose, serum levels of insulin and $IL-1{\beta}$, and DPP-4 activity, and suppressed the increase in body weight. On the contrary, various tissues including liver, kidney, and peripheral blood cells showed variable responses of DPP-4 to SB. Especially in the kidney, although DPP-4 activity was decreased by SB in HFD-induced obese mice, it caused an increase in mRNA expression of $TNF-{\alpha}$, IL-6, and $IL-1{\beta}$. The pro-inflammatory actions of SB in the kidney of HFD-induced obese mice were recapitulated by cultured mesangial cell experiments, in which SB stimulated the secretion of several cytokines from cells. Our results showed that SB has differential actions according to its treatment dose and the type of cells and tissues. Thus, further studies are required to evaluate its therapeutic relevance in metabolic diseases including diabetes and obesity.

• Journal of Ginseng Research
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• v.44 no.3
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• pp.475-482
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• 2020

Background: Active natural ingredients, especially small molecules, have recently received wide attention as modifiers used to treat neurodegenerative disease by promoting neurogenic regeneration of neural stem cell (NSC) in situ. 20(S)-protopanaxadiol (PPD), one of the bioactive ingredients in ginseng, possesses neuroprotective properties. However, the effect of PPD on NSC proliferation and differentiation and its mechanism of action are incompletely understood. Methods: In this study, we investigated the impact of PPD on NSC proliferation and neuronal lineage differentiation through activation of the Wnt/glycogen synthase kinase (GSK)-3β/β-catenin pathway. NSC migration and proliferation were investigated by neurosphere assay, Cell Counting Kit-8 assay, and EdU assay. NSC differentiation was analyzed by Western blot and immunofluorescence staining. Involvement of the Wnt/GSK3β/β-catenin pathway was examined by molecular simulation and Western blot and verified using gene transfection. Results: PPD significantly promoted neural migration and induced a significant increase in NSC proliferation in a time- and dose-dependent manner. Furthermore, a remarkable increase in anti-microtubule-associated protein 2 expression and decrease in nestin protein expression were induced by PPD. During the differentiation process, PPD targeted and stimulated the phosphorylation of GSK-3β at Ser9 and the active forms of β-catenin, resulting in activation of the Wnt/GSK-3β/β-catenin pathway. Transfection of NSCs with a constitutively active GSK-3β mutant at S9A significantly hampered the proliferation and neural differentiation mediated by PPD. Conclusion: PPD promotes NSC proliferation and neural differentiation in vitro via activation of the Wnt/GSK-3β/β-catenin pathway by targeting GSK-3β, potentially having great significance for the treatment of neurodegenerative diseases.

• Journal of Ginseng Research
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• v.45 no.6
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• pp.617-630
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• 2021

Chemotherapy-induced side effects affect the quality of life and efficacy of treatment of cancer patients. Current approaches for treating the side effects of chemotherapy are poorly effective and may cause numerous harmful side effects. Therefore, developing new and effective drugs derived from natural nontoxic compounds for the treatment of chemotherapy-induced side effects is necessary. Experiments in vivo and in vitro indicate that Panax ginseng (PG) and its ginsenosides are undoubtedly non-toxic and effective options for the treatment of chemotherapy-induced side effects, such as nephrotoxicity, hepatotoxicity, cardiotoxicity, immunotoxicity, and hematopoietic inhibition. The mechanism focus on anti-oxidation, anti-inflammation, and anti-apoptosis, as well as the modulation of signaling pathways, such as nuclear factor erythroid-2 related factor 2 (Nrf2)/heme oxygenase-1 (HO-1), P62/keap1/Nrf2, c-jun Nterminal kinase (JNK)/P53/caspase 3, mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinases (ERK), AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR), mitogen-activated protein kinase kinase 4 (MKK4)/JNK, and phosphatidylinositol 3-kinase (PI3K)/AKT. Since a systemic review of the effect and mechanism of PG and its ginsenosides on chemotherapy-induced side effects has not yet been published, we provide a comprehensive summarization with this aim and shed light on the future research of PG.