• Biomolecules & Therapeutics
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• v.23 no.6
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• pp.557-563
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• 2015

Skin aging is the most readily observable process involved in human aging. Ultraviolet B (UVB) radiation causes photo-oxidation via generation of reactive oxygen species (ROS), thereby damaging the nucleus and cytoplasm of skin cells and ultimately leading to cell death. Recent studies have shown that high levels of solar UVB irradiation induce the synthesis of matrix metalloproteinases (MMPs) in skin fibroblasts, causing photo-aging and tumor progression. The MMP family is involved in the breakdown of extracellular matrix in normal physiological processes such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes such as arthritis and metastasis. We investigated the effect of diphlorethohydroxycarmalol (DPHC) against damage induced by UVB radiation in human skin keratinocytes. In UVB-irradiated cells, DPHC significantly reduced expression of MMP mRNA and protein, as well as activation of MMPs. Furthermore, DPHC reduced phosphorylation of ERK and JNK, which act upstream of c-Fos and c-Jun, respectively; consequently, DPHC inhibited the expression of c-Fos and c-Jun, which are key components of activator protein-1 (AP-1, up-regulator of MMPs). Additionally, DPHC abolished the DNA-binding activity of AP-1, and thereby prevented AP-1-mediated transcriptional activation. These data demonstrate that by inactivating ERK and JNK, DPHC inhibits induction of MMPs triggered by UVB radiation.

• International Journal of Oral Biology
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• v.34 no.2
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• pp.61-72
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• 2009

Chios gum mastic (CGM) is a resin produced from the stem and leaves of Pistiacia lentiscus L var chia, a plant which grows only on Chios Island in Greece. CGM has been used for many centuries as a dietary supplement and folk medicine for stomach and duodenal ulcers in many Mediterranean countries and is known also to induce cell cycle arrest and apoptosis in some cancer cells. In this study, we further investigated the induction and mechanisms underlying the apoptotic response to CGM treatment in the SCC25 human tongue squamous cell carcinoma cell line. The viability of SCC25 cells, human normal keratinocytes (HaCaT cells) and human gingival fibroblasts (HGF-1 cells), and the growth inhibition of SCC25 cells were assessed by MTT assay and clonogenic assay, respectively. Staining with Hoechst and hemacolor dyes and TUNEL assays were employed to detect SCC25 cells undergoing apoptosis. SCC25 cells were treated with CGM, and this was followed by western blotting, immunocytochemistry, confocal microscopy, FACScan flow cytometry, MMP activity and proteasome activity analyses. CGM treatment of SCC25 cells was found to result in a time- and dosedependent decrease in cell viability, a dose-dependent inhibition of cell growth, and apoptotic cell death. Interestingly, CGM showed a remarkable level of cytotoxicity in SCC25 cells but not in normal cells. Tested SCC25 cells also showed several lines of apoptotic manifestation. Taken together, our present findings demonstrate that CGM strongly inhibits cell proliferation by modulating the expression of G1 cell cycle-related proteins and induces apoptosis via the proteasome, mitochondria and caspase cascades in SCC25 cells.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.16
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• pp.7285-7290
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• 2015

Background: Although radiotherapy is one of the most effective strategies in the treatment of cancers, it is associated with short and long term side effects on normal tissues. Zataria multiflora Boiss (Laminacea) (ZM) has several biological properties such as antioxidant and anti-inflammation activities.Here we investigated cell killing effects of a hydroalcoholic Zataria multiflora extract on cell death induced by ionizing radiation in a human glioblastoma cell line (A172) and human non-malignant fibroblasts (HFFF2) in vitro. Materials and Methods: A172 and HFFF2 cells were treated with a hydroalcoholic extract of dried aerial parts of Zataria multiflora at different concentrations (25, 50, 100, 150 and $200{\mu}g/ml$) and then exposed to ionizing radiation (IR). Cell proliferation and DNA fragmentation were evaluated. Thymol content in the extract was analyzed and quantified by HPLC methods. Results: A172 cell proliferation was significantly inhibited by ZM. The percentage cell survival was $91.8{\pm}8.57$ for cells treated with $200{\mu}g/ml$ of ZM extract alone while it was $76.0{\pm}4.27$ and $66.2{\pm}8.42$ for cells treated with ZM and exposed to IR at doses of 3Gy and 6Gy, respectively. Radiation-induced apoptosis in A172 cells was significantly increased following treatment with ZM at doses of $200{\mu}g/ml$. ZM extract did not exhibit any enhanced cell killing effects and apoptosis caused by IR on HFFF2 cells. Conclusions: These data show selective radiosensitization effects of ZM in A172 cells apparently due to increased radiation-induced apoptosis.

• Journal of Animal Reproduction and Biotechnology
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• v.37 no.4
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• pp.239-245
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• 2022

Protein and peptide candidates are screened to apply therapeutic application as a drug. Ensuring that these candidates are delivered and maximized effectiveness is still challenging and a variety of studies are ongoing. As drug delivery system vehicles, cell-penetrating peptide (CPP) can deliver various kinds of cargo into the cell cytosol. In a previous study, we developed Ara27 CPP, which are a zinc knuckle family protein of Arabidopsis, and confirmed internalization in human dermal fibroblasts and human dental pulp stem cells at low concentration with short time treatment condition without any toxicity. Ara27, an amphipathic CPP, could be modified and utilized in the biomedical field excluding the risk of toxicity. Therefore, we would like to confirm the non-toxic induced penetrating ability of Ara27 in various cell lines. The purpose of this study was to screen the cell internalization ability of Ara27 in various cell lines and to confirm Ara27 as a promising core CPP structure. First, Ara27 was screened to confirm non-toxicity concentration. Then, fluorescence-labeled Ara27 was treated on human normal cell lines, cancer cell lines and animal cell lines to identify the cellular internalization of Ara27. Ara27 was well intracellular localized in all cell lines and the intensity of fluorescence was remarkably increased in time pass manner. These results indicate that Ara27 has the potential as a core structure for applications in various drug delivery systems.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.2
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• pp.267-273
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• 2017

The p53-inducible gene 3 (PIG3), initially identified as a gene downstream of p53, plays an important role in the apoptotic process triggered by p53-mediated reactive oxygen species (ROS) production. Recently, several studies have suggested that PIG3 may play a role in various types of cancer. However, the functional significance of PIG3 in cancer remains unclear. Here, we found that PIG3 was highly expressed in human colon cancer cell lines compared to normal colon-derived fibroblasts. Therefore, we attempted to elucidate the functional role of PIG3 in colon cancer. PIG3 overexpression increases the colony formation, migration and invasion ability of HCT116 colon cancer cells. Conversely, these tumorigenic abilities were significantly decreased in in vitro studies with PIG3 knockdown HCT116 cells. PIG3 knockdown also attenuated the growth of mouse xenograft tumors. These results demonstrate that PIG3 is associated with the tumorigenic potential of cancer cells, both in vitro and in vivo, and could play a key oncogenic role in colon cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.5
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• pp.2123-2128
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• 2014

A current hurdle in cancer management is the intrinsic or acquired resistance of cancer cells to chemical agents that restricts the efficacy of therapeutic strategies. Accordingly, there is an increasing desire to discover new natural compounds with selective toxicity to combat malignancies. In present study, the cytotoxic and apoptosis-inducing activities of ferutinin, a terpenoid derivative from Ferula ovina, were investigated on human breast (MCF7) and bladder (TCC) cancer cells as well as normal fibroblasts (HFF3).The toxicity and DNA damage inducing effects of ferutinin were studied by MTT and comet assays, DAPI and PI staining and DNA laddering. The $IC_{50}$ values of ferutinin were identified and compared with routine prescribed drugs, doxorubicin and vincristine, by MTT test. Alkaline comet assay and DAPI staining revealed DNA damage due to ferutinin, which was significantly (p<0.001) higher in MCF7 and TCC than HFF3 cells. Apoptosis induction was evidenced by PI staining and DNA laddering. Our results suggest that ferutinin could be considered as an effective anticancer agent for future in vivo and clinical experiments.

• Macromolecular Research
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• v.15 no.7
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• pp.646-655
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• 2007

To achieve targeted drug delivery for chemotherapy, a ligand-mediated nanoparticulate drug carrier was designed, which could identity a specific receptor on the surfaces of tumor cells. Biodegradable poly(ethylene oxide)/poly$({\varepsilon}-caprolactone)$ (PEG/PCL) amphiphilic block copolymers coupled to biotin ligands were synthesized with a variety of PEG/PCL compositions. Block copolymeric nanoparticles harboring the anticancer drug paclitaxel were prepared via micelle formation in aqueous solution. The size of the biotin-conjugated PEG/PCL nanoparticles was determined by light scattering measurements to be 88-118 nm, depending on the molecular weight of the block copolymer, and remained less than 120 nm even after paclitaxel loading. From an in vitro release study, biotin-conjugated PEG/PCL nanoparticles containing paclitaxel evidenced sustained release profiles of the drug with no initial burst effect. The biotin-conjugated PEG/PCL block copolymer itself evidenced no significant adverse effects on cell viability at $0.005-1.0{\mu}g/mL$ of nanoparticle suspension regardless of cell type (normal human fibroblasts and HeLa cells). However, biotin-conjugated PEG/PCL harboring paclitaxel evidenced a much higher cytotoxicity for cancer cells than was observed in the PEG/PCL nanoparticles without the biotin group. These results showed that the biotin-conjugated nanoparticles could improve the selective delivery of paclitaxel into cancer cells via interactions with over-expressed biotin receptors on the surfaces of cancer cells.

• Journal of Microbiology and Biotechnology
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• v.33 no.9
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• pp.1250-1256
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• 2023

Herein, different extracts of Scenedesmus deserticola JD052, a green microalga, were evaluated in vitro as a potential anti-aging bioagent. Although post-treatment of microalgal culture with either UV irradiation or high light illumination did not lead to a substantial difference in the effectiveness of microalgal extracts as a potential anti-UV agent, the results indicated the presence of a highly potent compound in ethyl acetate extract with more than 20% increase in the cellular viability of normal human dermal fibroblasts (nHDFs) compared with the negative control amended with DMSO. The subsequent fractionation of the ethyl acetate extract led to two bioactive fractions with high anti-UV property; one of the fractions was further separated down to a single compound. While electrospray ionization mass spectrometry (ESI-MS) and nuclear magnetic resonance (NMR) spectroscopy analysis identified this single compound as loliolide, its identification has been rarely reported in microalgae previously, prompting thorough systematic investigations into this novel compound for the nascent microalgal industry.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.36 no.2
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• pp.137-143
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• 2010

Yuza (Citrus junos Sieb ex TANAKA) is a citrus fruit that is cultivated in northeast Asia. Citron is known for containing abundant antioxidants such as vitamin C, flavonoids, for example hesperidin and hesperetin, and terpenoids such as limononin. When mature citron is processed for tea or other beverage food products in Korea, massive amounts of seeds and pericarp are remained as waste. This study aimed to exploit the processed remnant of Citron for developing functional cosmetic applications. Ethanol extracts of Yuza seed and pericarp did not show significant radical scavenging activities measured by DPPH (2,2-diphenyl-1-picrylhydrazyl) method. But they contained significantly high phenolic compounds. Cultured human dermal fibroblasts and HaCaT keratinocytes were irradiated with 25 mJ UVB and the citron extracts were added to the medium of each culture. Cellular damages caused by UVB irradiation were prevented by the addition of the Yuza extract. In addition, the reduction of the enhanced MMP-1 expression after irradiation of UVB in human dermal fibroblasts was observed. Also the increased level of pro-inflammtory TNF-$\alpha$ in the UVB irradiated HaCaT cells was decreased. The collagen expression was enhanced by the extract. Yuza extract markedly inhibited melanin production from $\alpha$-MSH treated B16F1 melanoma cells. Melanin assay, tyrosinase zymography results indicated that Yuza extract had strong depigmenting activity. In conclusion, Yuza ethanol extracts have good anti-photoaging and strong anti-melanogenic efficacies.

• Journal of Life Science
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• v.33 no.4
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• pp.305-314
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• 2023

Ultraviolet B (UVB) irradiation causes skin diseases by inducing cellular oxidative stress, photoaging, and inflammation. This study aimed to investigate the protective effects of morin against UVB-induced oxidative stress in normal human dermal fibroblasts (NHDFs). Morin has been reported to be a potential therapeutic candidate for oxidative stress-mediated diseases, neurodegenerative diseases, and inflammation. Since morin has been identified as a potential antioxidant, we speculated that morin could alleviate UVB-induced apoptosis in NHDFs. Cell viability and intracellular reactive oxygen species (ROS) levels were measured using the MTT assay, H2DCFDA, and the DHE staining method, respectively. Lipid peroxidation and protein carbonyl formation were tested using ELISA kits. DNA fragmentation and comet assay were used to assess DNA damage. Apoptotic bodies were analyzed using Hoechst 33342 staining and TUNEL assay. The expression of apoptosis-related proteins was examined using Western blot analysis. Morin showed a cyto-protective effect by scavenging UVB-induced ROS, increasing the expression of antioxidant-related proteins and inhibiting UVB-induced oxidative alterations such as lipid peroxidation, protein carbonylation, and DNA damage. Morin protects against UVB-induced cell apoptosis by inhibiting Bcl-2-associated X protein, caspase-9, and caspase-3 expression, while increasing the expression of the anti-apoptotic protein Bcl-2. These effects of morin were conferred through decreased phosphorylation of p38 and c-Jun N-terminal kinase 1/2. The results demonstrated that morin may be developed as a preventive/therapeutic drug to be used to prevent UVB-induced skin damage.