• Journal of Life Science
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• v.16 no.6
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• pp.964-971
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• 2006

The cancer cells, characterized by local invasion and distant metastasis, are very dependant on extracellular matrix. The expression of matrix metalloproteinases (MMPs) has been implicated in the invasion and metastasis of cancer cells. Among the human MMPs, matirx metalloproteinase-2 (MMP-2) and matrix metalloproteinse-9 (MMP-9) are key enzymes that degrade type IV collagen of the matrix. Here, we studied the effect of disulfiram, an anti-tumor compound, on the suppression of the tumor invasion and the activity of MMP-2, MMP-9 in human osteosarcoma cells (U2OS). Disulfiram had the type IV collagenase inhibitory activity, the effect of inhibition of gene and protein expression, and these inhibitions were responsible for blocking invasion through cell mediated and non-cell mediated pathways. In conclusion, disulfiram inhibited expression of MMP-2 and MMP-9, and regulated the invasion of U2OS, Caki-1 and Caski. These observations raise the possibility of clinical therapeutic applications for disulfiram used as a potential inhibitor of cancer invasion.

• Journal of Life Science
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• v.25 no.5
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• pp.607-614
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• 2015

Cancers are the largest cause of mortality and morbidity all over the world. Cordycepin, an adenosine analog, is a major functional component of the Cordyceps species, which has been widely used in traditional Oriental medicine. Over the last decade, this compound has been reported to possess many pharmacological properties, such as an ability to enhance immune function, as well as anti-inflammatory, antioxidant and anti-cancer effects. Recently, numerous studies have reported interesting properties of cordycepin as a chemopreventive agent as well. There is an accumulating body of experimental evidences suggesting that cordycepin impedes cancer progression by promoting apoptosis, inducing cell cycle arrest, modulating intracellular signaling pathways, and inhibiting invasion and metastasis of cancer cells. In many cancer cell lines, cordycepin inhibits growth and cell cycle progression by inducing arrest of the G2/M phase, resulting from the inhibition of retinoblastoma protein phosphorylation and induction of cyclin-dependent kinase inhibitors. To induce apoptosis, cordycepin activates the extrinsic and intrinsic pathways, which promotes reactive oxygen species generation and the downstream activation of kinase cascades. Cordycepin also can activate alternative pathways to cell death such autophagy. In addition, cordycepin can inhibit the pro-metastatic processes of cancer cell detachment, migration, and invasion through a variety of mechanisms, including the nuclear factor-kappa B and activated protein-1 signaling pathways. In this review, we summarized the variety of action mechanisms by which cordycepin may mediate chemopreventive effects on cancer and discussed the potential of this natural product as a promising therapeutic inhibitor of cancer development.

• Journal of Life Science
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• v.21 no.3
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• pp.349-357
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• 2011

Inhibitors of EGFR (epidermal growth factor receptor) kinase activity may prove useful to therapeutically intervene in cancer and to treat other proliferative diseases. In this study, we investigated the inhibitive effects of two compounds named 63013 and 63033 possess a [1,4]-dioxino quinazoline structure that links the alkoxy side chains together and their structural characteristics are considered to allow better solubility than the dialkoxyquinazoline derivatives. The EGFR kinase activities of A431 human epidermoid carcinoma cells, stimulated by EGF were inhibited by treatment with 63013 and 63033 in a dose-dependent manner respectively. Consistent with the compound-mediated EGFR kinase suppression, the major EGF-related downstream target molecules, such as MEK1/2, MAPK p44/42, AKT and STAT3, were also suppressed by both compounds. Interestingly, both compounds led to cell growth inhibition at a lower concentration than that of Gefitinib (Iressa$^{(R)}$). Collectively, our study showed that both compounds may have good therapeutic potential as an EGFR kinase specific inhibitor to treat EGFR-related diseases.

• Journal of Life Science
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• v.20 no.11
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• pp.1603-1610
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• 2010

Fucoidans are sulfated fucosylated polymers from the cell wall of brown algae. We assessed the effects of Fucus evanescens fucoidan on ultraviolet-B (UVB)-induced expression of matrix metalloproteinase-1 (MMP-1) protein, mRNA, and promoter, and the phosphorylation of mitogen-activated protein kinases in vitro using an immortalized human keratinocyte cell line. Pretreatment with 10 and $100\;{\mu}g/ml$ fucoidan significantly inhibited UVB-induced MMP-1 protein, mRNA and promoter activity, compared to UVB irradiation alone. Extracellular signal regulated kinase activation was markedly inhibited by treatment with fucoidan, though c-JUN N-terminal kinase activity and p38 activation were only marginally affected by fucoidan. F. evanescens fucoidan may be a potential therapeutic agent for the prevention and treatment of skin photoaging.

• Journal of Life Science
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• v.23 no.1
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• pp.55-62
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• 2013

The objective of this study was to evaluate the anti-inflammation effect of extract of Carthamus tinctorious seed, on skin obtained from Gyeong buk, Korea. Regulatory mechanisms of cytokines and nitric oxide (NO) involved in immunological activity of Raw 264.7 cells. Tested cells were pretreated with 70% ethanol extracted of Carthamus tinctorious seed and further cultured for an appropriated time after the addition of lipopolyssacharide (LPS). During the entire experimental period, 5, 10, 25 and 50 ${\mu}g/ml$ of Carthamus tinctorious seed showed no cytotoxicity. In these concentrations, ethyl acetate layer of ethanol extracted Carthamus tinctorius seed (CT-E/E) inhibited the production of NO and prostaglandin $E_2$ ($PGE_2$), tumor necorsis factor-a (TNF-${\alpha}$), interleukin-$1{\beta}$ (IL-$1{\beta}$), interleukin-6 (IL-6) expression of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2). At a 50 ${\mu}g/ml$ level of CT-E/E, $PGE_2$, iNOS and COX-2 inhibition activity were shown 60%, 38%, and 42%, respectively. In addition, CT-E/E reduced the release of inflammatory cytokines including TNF-${\alpha}$, IL-$1{\beta}$ and IL-6. These results suggest that Carthamus tinctorious seed extracts may be a potential anti-inflammatory therapeutic agent due to the significant effects on inflammatory factors.

• Journal of Life Science
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• v.23 no.1
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• pp.38-43
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• 2013

The objective of this study was to evaluate the effect of the synthetic CopA3 peptide of Copris tripartitus on skin inflammation. Regulatory mechanisms of cytokines and nitric oxide (NO) are involved in the immunological activity of RAW 264.7 cells. Tested cells were treated with different concentrations of CopA3 and further cultured for an appropriate time after lipopolyssacharide (LPS) addition. During the entire experimental period, 5, 25, 50, and 100 ${\mu}g/ml$ of CopA3 had no cytotoxicity. At these concentrations, CopA3 inhibited tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin-$1{\beta}$ (IL-$1{\beta}$), and interleukin-6 (IL-6). CopA3 also inhibited the expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2). CopA3 inhibited the activity of iNOS and COX-2 by 41% and 59%, respectively, at 100 ${\mu}g/ml$. In addition, CopA3 reduced the release of inflammatory cytokines including TNF-${\alpha}$, IL-$1{\beta}$, and IL-6. These results suggest that CopA3 may have significant effects on inflammatory factors and that it may be a potential anti-inflammatory therapeutic agent.

• Journal of Life Science
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• v.27 no.7
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• pp.834-839
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• 2017

Propolis is a natural product collected from plants by honey bees product used extensively in traditional medicine for its antioxidant, anti-inflammatory, immunomodulatory and anti-cancer effects. Propolis exhibits a broad spectrum of biological activities because it is a complex mixture of natural substances. Ovarian cancer is the second most common newly diagnosed cancer from all cancers among women in Korea and the leading cause of death from gynecological malignancies. While most ovarian cancer patients initially respond to surgical debulking and chemotherapy, patients later succumb to the disease. Thus, there is an urgent need to test novel therapeutic agents to counteract the high mortality rate associated with ovarian cancer. In this study, we investigated the anti-cancer properties and the active mechanism of Australian propolis in human epithelial ovarian cancer A2780 cells. Our data revealed that propolis showed a cytotoxic activity in a dose-dependent manner. Flow cytometric analysis for cell cycle arrest and apoptosis using propidium iodide staning and annexin V-FITC indicated that propolis could induce cycle arrest in the G0/G1 phase and apoptosis in a dose-dependent manner on human epithelial ovarian cancer cells. These results suggest that the Australian propolis is potential alternative agent on ovarian cancer prevention and treatment.

• Journal of Life Science
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• v.27 no.10
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• pp.1225-1231
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• 2017

Disruptive expression patterns of the circadian clock genes are highly associated with many human diseases, including cancer. Cell cycle and proliferation is linked to a circadian rhythm; therefore, abnormal clock gene expression could result in tumorigenesis and malignant development. The molecular network of the circadian clock is based on transcriptional and translational feedback loops orchestrated by a variety of clock activators and clock repressors. The expression of 10~15% of the genome is controlled by the overall balance of circadian oscillation. Among the many clock genes, Period 1 (Per1) and Period 2 (Per2) are clock repressor genes that play an important role in the regulation of normal physiological rhythms. It has been reported that PER1 and PER2 are involved in the expression of cell cycle regulators including cyclins, cyclin-dependent kinases (CDKs), and CDK inhibitors. In addition, correlation of the down-regulation of PER1 and PER2 with development of many cancer types has been revealed. In this review, we focused on the molecular function of PER1 and PER2 in the circadian clock network and the transcriptional and translational targets of PER1 and PER2 involved in cell cycle and tumorigenesis. Moreover, we provide information suggesting that PER1 and PER2 could be promising therapeutic targets for cancer therapies and serve as potential prognostic markers for certain types of human cancers.

• Journal of the Korean Society of Food Science and Nutrition
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• v.37 no.6
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• pp.714-720
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• 2008

Cordyceps militaris is a medicinal fungus which has been used for patient suffering from cancer in Oriental medicine. It was previously reported that C. militaris extracts are capable of inhibiting tumor growth and inducing apoptosis; however, the anti-poliferative effects of human cancer cells have been poorly understood. In this study, to elucidate the anti-cancer mechanisms of human cancer cells by treatment with aqueous extract of C. militaris (AECM), we investigated the anti-proliferative effects of AECM in human hepatocarcinoma Hep3B cells. AECM treatment inhibited the growth of Hep3B cells and induced the apoptotic cell death in a concentration-dependent manner such as formation of apoptotic bodies and increased populations of apoptotic-sub G1 phase. The induction of apoptosis by AECM was connected with a proteolytic activation of caspase-3 and caspase-8. and concomitant degradation of poly (ADP-ribose) polymerase (PARP) and ${\beta}$-catenin proteins. Furthermore, caspase-3 inhibitor, z-DEVD-fmk, significantly inhibited AECM-induced apoptosis demonstrating the important role of caspase-3 in the bserved cytotoxic effect. Taken together, these findings suggest that AECM-induced inhibition of human hepatocarcinoma cell proliferation is associated with the induction of apoptotic cell death via activation of caspase-3 and C. militaris may have therapeutic potential in human cancer.

• Microbiology and Biotechnology Letters
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• v.38 no.1
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• pp.105-111
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• 2010

Caesalpinia sappan L. has long been commonly used in oriental folk medicines to treat diseases. To investigate the antibacterial effects from C. sappan L. heart wood, the MeOH soluble extract was successively fractionated by using hexane, $CHC1_3$, EtOAc, BuOH, MeOH, and $H_2O$. Among of these extracts, the EtOAc fraction which partitioned to 3.94% of the highest yields was to be the most active against all human pathogenic bacteria in this experiment. In addition, the antibacterial activities of the EtOAc fraction were more effective against Gram (+) bacteria compared to those against Gram (-) bacteria, which showed difference of the antibacterial activities against Gram (-) bacteria. To confirm the identity of the active substances, the EtOAc fraction was further separated by silica gel adsorption column, high performance liquid chromatography, and 98.48% purity of brazilin (1.67 mg)/EtOAc (10 mg) fraction was obtained from 300 g of C. sappan L. heart wood. The isolated active substance was a single compound of yellow crystalline, and was identified as brazilin ($C_{16}H_{14}O_5$) by MS, and $^lH$-NMR and $^{13}C$-NMR. These results suggest that the brazilin in the EtOAc fraction from MeOH extract of C. sappan L. has a potential as a natural therapeutic agent against human pathogenic Gram (+) bacteria such as Staphylococcus aureus.