• Journal of Oral Medicine and Pain
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• v.34 no.3
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• pp.261-276
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• 2009

Lactacystin, a microbial natural product synthesized by Streptomyces, has been commonly used as a selective proteasome inhibitor in many studies. Proteasome inhibitors is known to be preventing the proliferation of cancer cells in vivo as well as in vitro. Furthermore, proteasome inhibitors, as single or combined with other anticancer agents, are suggested as a new class of potential anticancer agents. This study was undertaken to examine in vitro effects of cytotoxicity and growth inhibition, and the molecular mechanism underlying induction of apoptosis in SCC25 human tongue sqaumous cell carcinoma cell line treated with lactacystin. The viability of SCC25 cells, human normal keratinocytes (HaCaT cells) and human gingiva fibroblasts (HGF-1 cells), and the growth inhibition of SCC25 cells were assessed by MTT assay and clonogenic assay respectively. The hoechst staining, hemacolor staining and TUNEL staining were conducted to observe SCC25 cells undergoing apoptosis. SCC25 cells were treated with lactacystin, and Western blotting, immunocytochemistry, confocal microscopy, FAScan flow cytometry, MMP activity, and proteasome activity were performed. Lactacystin treatment of SCC25 cells resulted in a time- and does-dependent decrease of cell viability and a does-dependent inhibition of cell growth, and induced apoptotic cell death. Interestingly, lactacytin remarkably revealed cytotoxicity in SCC25 cells but not normal cells. And tested SCC25 cells showed several lines of apoptotic manifestation such as nuclear condensation, DNA fragmentation, the reduction of MMP and proteasome activity, the decrease of DNA contents, the release of cytochrome c into cytosol, the translocation of AIF and DFF40 (CAD) onto nuclei, the up-regulation of Bax, and the activation of caspase-7, caspase-3, PARP, lamin A/C and DFF45 (ICAD). Flow cytometric analysis revealed that lactacystin resulted in G1 arrest in cell cycle progression which was associated with up-regulation in the protein expression of CDK inhibitors, $p21^{WAF1/CIP1}$ and $p27^{KIP1}$. We presented data indicating that lactacystin induces G1 cell cycle arrest and apoptois via proteasome, mitochondria and caspase pathway in SCC25 cells. Therefore our data provide the possibility that lactacystin could be as a novel therapeutic strategy for human tongue squamous cell carcinoma.

• Food Science and Preservation
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• v.21 no.2
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• pp.264-275
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• 2014

This study evaluated the improving efficacy of Lespedeza cuneata ethanol extract on skin photoaging induced by ultraviolet (UV) irradiation. The total polyphenol and flavonoid contents of the extract were respectively $134.98{\pm}1.70$ and $16.20{\pm}0.05$ mg/g, respectively. The superoxide anion radical scavenging activity and electron-donating ability of the extract were shown to be dependent on concentration, and the antioxidant ability was shown to be more effective in superoxide anion radical scavenging activity than in electron-donating ability under the same concentration conditions. In the in vivo test conducted using hairless mouse with skin photoaging induced by UVB irradiation, the skin erythema of the groups treated with the extract (AS) reduced to 28% of the control, and the skin moisture content increased to 131%.. The extract treatment of the UV-damaged skin improved the morphological and histopathological state of the skin. Furthermore, the SOD, GST and CAT activities in the skin tissue of the AS group increased, and the XO activity and TBARS generation decreased. With regard to the genes related to the photoaging skin, the expression of PAK, p38, c-Fos, c-Jun, TNF-${\alpha}$ and MMP-3 in the skin of the AS group were found to have decreased. It was therefore concluded that Lespedeza cuneata ethanol extract can reduce wrinkle formation in the skin due to the regulation of the gene expression caused by the exposure to UVB light.

• Food Science and Preservation
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• v.19 no.3
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• pp.393-399
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• 2012

In this study, the antioxidant and anti-wrinkling effects of extracts from Aruncus diocius var. kamtschaticus (ADV) were investigated. According to the results, the ethanol extract has better antioxidant and anti-wrinkling effects than the water extract. The amounts of total polyphenol and flavonoid compounds in the ethanol extract were 122 and 36 mg/g, respectively, while those in the water extract were 87 and 26 mg/g. The antioxidant activities of the ethanol and water extracts were 395 and 4,682 ${\mu}g/mL$ as the $RC_{50}$ values for the DPPH radical scavenging activity, and 227 and 366 ${\mu}g/mL$ for the $ABTS^+$ radical scavenging activity, respectively. The reducing power of the ethanol extract (1.58 at 2 mg/mL) was higher than that of the water extract (0.88 at 2 mg/mL). The astringent activities of the ethanol and water extracts were 91.27 and 16.35% at 10 mg/mL, respectively. Furthermore, the ADV ethanol extract treatment of the fibroblast cell after UV irradiation resulted in increased cell viability (10% at 100 ${\mu}g/mL$) and collagen biosynthesis (33% at 100 ${\mu}g/mL$), with a lowering in the MMP-1 expression level (16.8 % at 100 ${\mu}g/mL$). These results demonstrate that AVD provides a remarkable and significant tensor and anti-wrinkling effect on the skin, which could be of a great use in anti-aging skin care products.

• Journal of Life Science
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• v.27 no.9
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• pp.975-985
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• 2017

To investigate the beneficial effects of an agar gel mask (AGM) on UV-induced photoaging, SKH-1 hairless mice were treated with a topical application of AGM and an AGM dipped in essence (AGMdE). The mice were divided into an no radiation group, UV + AGM, UV + AGMdE, and UV + vehicle (PBS) treatment groups. Alterations in skin wrinkles, skin phenotype, histological structures, oxidative status, and toxicity were then evaluated during 4 weeks of exposure. The topical application of AGM and AGMdE inhibited wrinkle formation, suppressed the erythema index, prevented transepidermal water loss, and enhanced skin hydration. In addition, epidermal thickness recovered to a similar level as that in the no irradiation group in the UV + AGM and UV + AGMdE treatment groups compared with the UV + vehicle (distilled water) group. Furthermore, the expression levels of matrix metalloproteinase-1 (MMP-1) and tyrosinase were reduced in the UV + AGM and UV + AGMdE treatment groups, although the highest level varied. Moreover, superoxide dismutase (SOD) activity was significantly lower in the UV + AGM and UV + AGMdE treatment groups as compared with the UV + vehicle group. No significant alterations induced by most toxic compounds were measured in serum biochemical markers and liver and kidney histological features of the UV + AGM and UV + AGMdE treatment groups. These results suggest that AGM may protect against skin aging by regulating skin morphology, histopathological structures, and oxidative conditions.

• Korean Journal of Food Science and Technology
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• v.51 no.4
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• pp.379-392
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• 2019

The current study investigated the effect of Gabjubaekmok (Diospyros kaki) ethanolic extract (GEE) on $H_2O_2$-induced human neuroblastoma MC-IXC cells and amyloid beta $(A{\beta})_{1-42}$-induced ICR (Institute of Cancer Research) mice. GEE showed significant antioxidant activity that was evaluated based on ABTS, DPPH scavenging activity, and inhibition of malondialdehyde (MDA) and acetylcholinesterase activity. Further, GEE inhibited ROS production and increased cell viability in $H_2O_2$-induced MC-IXC cells. Administration of GEE ameliorated the cognitive dysfunction on $A{\beta}$-induced ICR mice as evaluated using Y-maze, passive avoidance, and Morris water maze tests. Results of ex vivo test using brain tissues showed that, GEE protected the cholinergic system and mitochondrial functions by increasing the levels of antioxidants such as ROS, mitochondrial membrane potential (MMP), and adenosine triphosphate (ATP) against $A{\beta}$-induced cognitive dysfunction. Moreover, GEE decreasd the expression levels of apoptosis-related proteins such as $TNF-{\alpha}$, p-JNK, p-tau, BAX and caspase 3. While, expression levels of p-Akt and $p-GSK3{\beta}$ increased than $A{\beta}$ group. Finally, gallic acid was identified as the main compound of GEE using high performance liquid chromatography.

• Korean Journal of Plant Resources
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• v.32 no.4
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• pp.255-263
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• 2019

Glycyrrhizae radix is one of the most frequently prescribed ingredients in Oriental medicine, and Glycyrrhizae radix extract has been shown to exert anti-cancer effects. However, the cellular and molecular mechanisms of programed cell death (apoptosis) by Glycyrrhizae radix are poorly defined. In the present study, it was examined the molecular mechanisms of apoptosis by water extracts of Glycyrrhizae radix (GRW) in human bladder T24 cancer cells. It was found that GRW could inhibit the cell growth of T24 cells in a concentration-dependent manner, which was associated with the induction of apoptotic cell death, as evidenced by the formation of apoptotic bodies, DNA fragmentation and increased populations of annexin-V positive cells. The induction of apoptotic cell death by GRW was connected with an up-regulation of pro-apoptotic Bax protein expression and down-regulation of anti-apoptotic proteins (Bcl-2 and Bcl-xL), and inhibition of apoptosis family proteins (XIAP, cIAP-1 and cIAP-2). In addition, apoptosis-inducing concentrations of GRW induced the activation of caspase-9, an initiator caspase of the mitochondrial-mediated intrinsic pathway, and caspase-3, accompanied by proteolytic degradation of PARP. GRW also induced apoptosis via a death receptor-mediated extrinsic pathway by caspase-8 activation, resulting in the down-regulation of total Bid and suggesting the existence of cross-talk between the extrinsic and intrinsic pathways. Taken together, the present results suggest that GRW may be a potential chemotherapeutic agent for the control of human bladder cancer cells.

• Food Science and Industry
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• v.53 no.1
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• pp.2-32
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• 2020

In recent years, significant importance has been given to chitooligosaccharides (COS) due to its potent notable biological applications. COS can be derived from chitosan which is commonly produced by partially hydrolyzed products from crustacean shells. In order to produce COS, there are several approaches including chemical and enzymatic methods which are the two most common choices. In this regard, several new methods were intended to be promoted which use the enzymatic hydrolysis with a lower cost and desired properties. Hence, the dual reactor system has gained more attention than other newly developed technologies. Enzymatic hydrolysis derived COS possesses important biological activities such as anticancer, antioxidant, anti-hypersentive, anti-dementia (Altzheimer's disease), anti-diabeties, anti-allergy, anti-inflammatory, etc. Results strongly suggest that properties of COS can be potential materials for nutraceutical, pharmaceutical, and cosmeceutical product development.

• Korean Journal of Food Science and Technology
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• v.53 no.4
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• pp.399-407
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• 2021

Wrinkle formation and dryness are the most well-known symptoms of skin aging. This study investigated skin anti-aging and moisturizing effects of Mugunghwa (Hibiscus syriacus L.), the national flower of Korea. The effect of H. syriacus L. flower extract was examined in skin cells originating from humans in vitro and in hairless mice exposed to UVB in vivo. The in vivo study results showed that skin hydration-related factors such as involucrin, filaggrin, HAS1, HYAL1, and matrix metalloproteinase-I (a primary skin photoaging factor) were regulated by H. syriacus L. Additionally, epidermal thickness and collagen disruption, which resulted in wrinkle formation and skin dryness, were ameliorated by oral administration of H. syriacus L. These results indicate that H. syriacus L. flowers can play important roles in preventing aging and promoting skin moisturizing.

• Journal of Life Science
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• v.31 no.4
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• pp.418-424
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• 2021

Skin inflammation (dermatitis) is caused by varying skin damage due to ultraviolet radiation and microbial infection. Currently prescribed drugs for dermatitis include anti-histamine and steroid drug classes that soothe inflammation. However, incorrect or prolonged use of steroids can cause weakening of skin barriers as well as osteoporosis. Therefore, treating dermatitis with a drug that has minimal side effects is important. Statins, also known as 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, are cholesterol-lowering drugs that have been widely treated for hyperlipidemia and cardiovascular diseases. Interestingly, recent studies have shown the anti-inflammatory effects of statins in both experimental and clinical models for of osteoarthritis. This study investigated the possible anti-inflammatory effects of atorvastatin and fluvastatin in human keratinocytes (HaCaT cells), which are crucial components of skin barriers. Stimulation of HaCaT cells with IL-1β increased the expression of the COX2 protein, a major player of inflammatory responses. However, this induction of the COX2 protein was downregulated by pretreatments with atorvastatin and fluvastatin. Treatment with IL-1ß-induced the upregulation of other inflammatory genes (such as iNOS and MMP-1) and these expressions were similarly lowered by these two statin drug treatments. Taken together, these results indicated that atorvastatin and fluvastatin can reduce IL-1β-induced inflammatory responses in HaCaT cells. In conclusion, the findings suggest that atorvastatin and fluvastatin can be potential modulators for ameliorating skin inflammation.

• Radiation Oncology Journal
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• v.19 no.2
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• pp.171-180
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• 2001

Purpose : Expression of TIMP, intrinsic inhibitor of MMP, is regulated by signal transduction in response to genotoxins and is likely to be an important step in metastasis, angiogenesis and wound healing after ionizing radiation. Therefore, we studied radiation mediated TIMP expression and its mechanism in head and neck cancer cell lines. Materials and Methods : Human head and neck cancer cell lines established at Asan Medical Center were used and radiosensitivity $(D_0)$, radiation cytotoxicity and metastatic potential were measured by clonogenic assay, n assay and invasion assay, respectively. The conditioned medium was prepared at 24 hours and 48 hours after 2 Gy and 10 Gy irradiation and expression of TIMP protein was measured by Elisa assay with specific antibodies against human TIMP. hTIMP1 promoter region was cloned and TIMP1 luciferase reporter vector was constructed. The reporter vector was transfected to AMC-HN-1 and -HN-9 cells with or without expression vector Ras, then the cells were exposed to radiation or PMA, PKC activator. EMSA was peformed with oligonucleotide (-59/-53 element and SP1) of TIMP1 promoter. Results : $D_0$ of HN-1, -2, -3, -5 and -9 cell lines were 1.55 Gy, 1.8 Gy, 1.5 Gt, 1.55 Gy and 2.45 Gy respectively. n assay confirmed cell viability, over $94\%$ at 24hrs, 48hrs after 2 Gy irradiation and over 73% after 10 Gy irradiation. Elisa assay confirmed that cells secreted TIMP1, 2 proteins continuously. After 2 Gy irradiation, TIMP2 secretion was decreased at 24hrs in HN-1 and HN-9 cell lines but after 10 Gy irradiation, it was increased in all cell lines. At 48hrs after irradiation, it was increased in HN-1 but decreased in HN-9 cells. But the change in TIMP secretion by RT was mild. The transcription of TIMP1 gene in HN-1 was induced by PMA but in HN-9 cell lines, it was suppressed. Wild type Ras induced the TIMP-1 transcription by 20 fold and 4 fold in HN-1 and HN-9 respectively. The binding activity to -59/-53, AP1 motif was increased by RT, but not to SP1 motif in both cell lines. Conclusions : We observed the difference of expression and activity of TIMPs between radiosensitive and radioresistant cell line and the different signal transduction pathway between in these cell lines may contribute the different radiosensitivity. Further research to investigate the radiation response and its signal pathway of TIMPs is needed.