• Journal of Acupuncture Research
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• v.31 no.2
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• pp.75-85
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• 2014

Objectives : We investigated whether bee venom(BV) inhibit cell growth through enhancement of death receptor expressions in the human cervix cancer C33A cells. Methods : BV($1{\sim}5{\mu}g/ml$) inhibited the growth of cervix cancer C33A cells by the induction of apoptotic cell death in a dose dependent manner. Results : Consistent with apoptotic cell death, expression of Fas, death receptor(DR) 3, 4, 5 and 6 was increased concentration dependently in the cells. Moreover, Fas, DR3 and DR6 revealed more sensitivity to BV. Thus, We reconfirmed whether they actually play a critical role in anti-proliferation of cervix cancer C33A cells. Consecutively, expression of DR downstream pro-apoptotic proteins including caspase-8, -3, -9 was upregulated and Bax was concomitantly overwhelmed the expression of Bcl-2. NF-${\kappa}B$ were also inhibited by treatment with BV in C33A cells. Conclusions : These results suggest that BV could exert anti-tumor effect through induction of apoptotic cell death in human cervix cancer C33A cells via enhancement of death receptor expression, and that BV could be a promising agent for preventing and treating cervix cancer.

• Radiation Oncology Journal
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• v.19 no.2
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• pp.153-162
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• 2001

Purpose : The mechanical insights of death of cancer cells by ionizing radiation are not of yet clearly defined. Recent evidences have demonstrated that radiation therapy may induce cell death via activation of signaling pathway for apoptosis in target cells. This study is designed whether ionizing radiation may activate the signaling cascades of apoptosis including caspase family cysteine pretenses, $Bcl_2/Bax$, cytochrome c and Fas/Fas-L in target cells. Materials and Methods : HL-60 cells were irradiated in vitro with 6 MV X-ray at dose ranges from 2 Gy to 32 Gy. The cell viability was tested by M assay and the extent of apoptosis was determined using agarose gel electrophoresis. The activities of caspase proteases were measured by proteolytic cleavages of substrates. Western blot analysis was used to monitor PARP, Caspase-3, Cytochrome-c, Bcl-2, Bax, Fas and Fas-L. Results : Ionizing radiation decreases the viability of HL-60 cells in a time and dose dependent manner. Ionizing radiation-induced death in HL-60 cells is an apoptotic death which is revealed as characteristic ladder-pattern fragmentation of genomic DNA over 16 Gy at 4 hours. ionizing radiation induces the activation of caspase-2, 3, 6, 8 and 9 of HL-60 cells in a time-dependent manner. The activation of caspase-3 pretense is also evidenced by the digestion of poly (ADP-ribose) polymerase and procaspase 3 with 16Gy ionizing irradiation. Anti-apoptotic Bcl2 expression is decreased but apoptotic Bax expression is increased with mitochondrial cytochrome c release in a time- dependent manner. In addiiton, expression of Fas and Fas-L is also increased in a time dependent manner. Conclusion : These data suggest that ionizing radiation-induced apoptosis is mediated by the activation of various signaling pathways including caspase family cysteine proteases, $Bcl_2/Bax$, Fas and Fas-L in a time and dose dependent manner.

• Journal of Life Science
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• v.25 no.5
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• pp.515-522
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• 2015

Treculia africana Decne, a breadfruit species, is native to many parts of West and Tropical Africa. The breadfruit belongs to the family Moraceae and is one of the four members of the genera Treculia. The crude extract of T. africana has been used in folk medicine as an anti-inflammatory agent for various ailments, such as whooping cough. In this study, we evaluated the anti-oxidative and anti-cancer activities of the methanol extract of T. africana Decne (META) and the molecular mechanisms of its anti-cancer effects in human colon carcinoma HT29 cells. The META exhibited anti-oxidative activity through a DPPH radical scavenging capacity and inhibited cell growth in a dose-dependent manner in HT29 cells. META treatment induced apoptosis of HT29 cells, showing an increase in the percentage of both SubG1 cells and Annexin V-positive cells and the formation of apoptotic bodies in a dose-dependent manner. META-mediated apoptosis was associated with the up-regulation of the death receptor FAS and Bax and a decrease in the Bcl-2 expression. META-treated HT29 cells also showed the release of cytochrome c from the mitochondria into the cytosol, activation of caspase-3, caspase-8, and caspase-9, and proteolytic cleavage of poly ADP-ribose polymerase (PARP). These findings suggest META may exert an anti-cancer effect in HT29 cells by inducing apoptosis through both intrinsic and extrinsic pathways.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.5783-5788
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• 2013

Trigonella foenum in graecum (Fenugreek) is a traditional herbal plant used to treat disorders like diabetes, high cholesterol, wounds, inflammation, gastrointestinal ailments, and it is believed to have anti-tumor properties, although the mechanisms for the activity remain to be elucidated. In this study, we prepared a methanol extract from Fenugreek whole plants and investigated the mechanism involved in its growth-inhibitory effect on MCF-7 human breast cancer cells. Apoptosis of MCF-7 cells was evidenced by investigating trypan blue exclusion, TUNEL and Caspase 3, 8, 9, p53, FADD, Bax and Bak by real-time PCR assays inducing activities, in the presence of FME at $65{\mu}g/mL$ for 24 and 48 hours. FME induced apoptosis was mediated by the death receptor pathway as demonstrated by the increased level of Fas receptor expression after FME treatment. However, such change was found to be absent in Caspase 3, 8, 9, p53, FADD, Bax and Bak, which was confirmed by a time-dependent and dose-dependent manner. In summary, these data demonstrate that at least 90% of FME induced apoptosis in breast cell is mediated by Fas receptor-independently of either FADD, Caspase 8 or 3, as well as p53 interdependently.

• Journal of Korean Medicine for Obesity Research
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• v.20 no.1
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• pp.1-9
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• 2020

Objectives: Artemisinin and its derivatives extracted from Artemisia annua, a Chinese herbal medicine, have variable biological effects due to structural differences. Up to date, the anti-obesity effect of dihydroartemisinin (DHA), a derivative of artemisinin, is unknown. The purpose of this study was to investigate the anti-adipogenic and lipolytic effects of DHA on 3T3-L1 preadipocytes. Methods: Oil Red O staining and AdipoRed assay were used to measure lipid accumulation and triglyceride (TG) content in 3T3-L1 cells, respectively. Cell count analysis was used to determine the cytotoxicity of 3T3-L1 cells. Western blot and real-time reverse transcription polymerase chain reaction analyses were used to analyze the expression of protein and mRNA in 3T3-L1 cells, respectively. Results: DHA at 5 μM markedly inhibited lipid accumulation and reduced TG content in differentiating 3T3-L1 cells with no cytotoxicity. Furthermore, DHA at 5 μM inhibited the expression of CCAAT/enhancer-binding protein-α (C/EBP-α), peroxisome proliferator-activated receptor-γ (PPAR-γ), fatty acid synthase (FAS), and perilipin A as well as the phosphorylation of signal transducer and activator of transcription-3 (STAT-3) in differentiating 3T3-L1 cells. Moreover, while DHA at 5 μM had no effect on the mRNA expression of adiponectin, it strongly suppressed that of leptin in differentiating 3T3-L1 cells. However, DHA at 5 μM had no lipolytic effect on differentiated 3T3-L1 cells, as assessed by no enhancement of glycerol release. Conclusions: These results demonstrate that DHA at 5 μM has a strong anti-adipogenic effect on differentiating 3T3-L1 cells through the reduced expression and phosphorylation of C/EBP-α, PPAR-γ, FAS, perilipin A, and STAT-3.

• Journal of Korean Medicine for Obesity Research
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• v.20 no.2
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• pp.109-121
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• 2020

Objectives: Tanshinone I is a bioactive constituent in Salvia miltiorrhiza. At present, the anti-obesity effect and mechanism of tanshinone I are not fully understood. Here we investigated the effect of tanshinone I on lipid accumulation in 3T3-L1 preadipocytes and zebrafish. Methods: Lipid accumulation and triglyceride (TG) content in 3T3-L1 cells were determined by Oil Red O staining and AdipoRed assay, respectively. The expression and phosphorylation levels of adipogenic/lipogenic proteins in 3T3-L1 cells were evaluated by Western blotting. The messenger RNA (mRNA) expression levels of adipogenic/lipogenic markers and leptin in 3T3-L1 cells were measured by reverse transcription polymerase chain reaction (RT-PCR). Lipid accumulation in zebrafish was assessed by LipidGreen2 staining. Results: Tanshinone I at 5 μM largely blocked lipid accumulation and reduced TG content in differentiating 3T3-L1 cells. Furthermore, tanshinone I decreased the expression of CCAAT/enhancer-binding protein-α (C/EBP-α), peroxisome proliferator-activated receptor-γ (PPAR-γ), fatty acid synthase (FAS), acetyl CoA carboxylase (ACC), and perilipin A but also the phosphorylation of signal transducer and activator of transcription-3 (STAT-3) in differentiating 3T3-L1 cells. In addition, tanshinone I increased the phosphorylation of adenosine 3',5'-cyclic monophosphate (cAMP)-activated protein kinase (AMPK) while decreased the intracellular adenosine triphosphate (ATP) content with no change in the phosphorylation and expression of liver kinase-B1 in differentiating 3T3-L1 cells. Importantly, tanshinone I also reduced the extent of lipid deposit formation in developing zebrafish. Conclusions: These findings demonstrate that tanshinone I has strong anti-adipogenic effects on 3T3-L1 cells and reduces adiposity in zebrafish, and these anti-adipogenic effect in 3T3-L1 cells are mediated through control of C/EBP-α, PPAR-γ, STAT-3, FAS, ACC, perilipin A, and AMPK.

• Fisheries and Aquatic Sciences
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• v.25 no.5
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• pp.251-263
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• 2022

Sea cucumbers are worm-like, leathery bodied, benthic, marine organisms with a branched gonad. There are over 900 species, and these organisms are capable of changing their mechanical state, regenerating their small appendages, and digestive tract. Additionally, sea cucumbers possess both commercial and therapeutical value. Furthermore, it is thought that the metabolites these organisms possess may give rise to their therapeutical value. The use of sea cucumbers in therapy can be traced back to the Ming dynasty, where they were eaten for their tonic properties against constipation, hypertension, and rheumatism. A plethora of studies have been conducted, whereby different metabolites were extracted from sea cucumbers and tested for different therapeutic properties. Herein, we review and discuss the anti-cancer, anti-microbial, anti-coagulant, anti-diabetic, antioxidant, and anti-inflammatory properties of the sea cucumber by assessing literature on PubMed and Google Scholar. Furthermore, the genome and epigenome of these remarkable species is discussed. With the immense data supporting the therapeutic properties of sea cucumbers, further studies are warranted, in order to develop novel and innovative therapeutic compounds for the benefit of human health from these fascinating marine organisms.

• Fisheries and Aquatic Sciences
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• v.8 no.2
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• pp.51-55
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• 2005

We measured the anti-attachment activity of allelochemical and antifouling substances using monospores from Porphyra yezoensis Ueda as an assay. Methanol or aqueous extracts ($20/{\mu}g/mL$) from 32 seaweeds were added to monospore suspensions. Methanol extracts of Corallina pilulifera, Ishige sinicola, Sargassum horneri, and Sargassum sagamianum inhibited attachment $by\;>90\%$ compared to the reference. Phenolic compounds fractionated from S. sagamianum caused the most potent inhibition. P. yezoensis monospores also showed significant sensitivity to known allelochemical and algicidal compounds.

• Fisheries and Aquatic Sciences
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• v.15 no.1
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• pp.73-76
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• 2012

Dichloromethane, ethanol, and boiling water extracts of the brown alga Ecklonia cava were examined in vivo for their antipyretic, analgesic, and anti-inflammatory activities in mice. These activities were evaluated by yeast-induced pyrexia, tail-flick test, and phorbol myristate acetate-induced inflammation (edema, erythema, and blood flow). Ethanol extract of E. cava (0.4 mg/ear) inhibited the inflammatory symptoms of mouse ear edema, erythema, and blood flow by 82.6%, 69.0%, and 65.4%, respectively. This extract also demonstrated potent analgesic activity. No acute toxicity was observed after p.o. administration of each extract (5 g/kg bw). These in vivo data are in agreement with the claims of the health care industry and indigenous medicine that E. cava is an effective remedy for inflammation-related symptoms.

• Nutrition Research and Practice
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• v.16 no.3
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• pp.330-343
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• 2022

BACKGROUND/OBJECTIVES: Zanthoxylum schinifolium is traditionally used as a spice for cooking in East Asian countries. This study was undertaken to evaluate the anti-proliferative potential of ethanol extracts of Z. schinifolium leaves (EEZS) against human bladder cancer T24 cells. MATERIALS/METHODS: Subsequent to measuring the cytotoxicity of EEZS, the anti-cancer activity was measured by assessing apoptosis induction, reactive oxygen species (ROS) generation, and mitochondrial membrane potential (MMP). In addition, we determined the underlying mechanism of EEZS-induced apoptosis through various assays, including Western blot analysis. RESULTS: EEZS treatment concentration-dependently inhibited T24 cell survival, which is associated with apoptosis induction. Exposure to EEZS induced the expression of Fas and Fas-ligand, activated caspases, and subsequently resulted to cleavage of poly (ADP-ribose) polymerase. EEZS also enhanced the expression of cytochrome c in the cytoplasm by suppressing MMP, following increase in the ratio of Bax:Bcl-2 expression and truncation of Bid. However, EEZS-mediated growth inhibition and apoptosis were significantly diminished by a pan-caspase inhibitor. Moreover, EEZS inhibited activation of the phosphoinositide 3-kinase (PI3K)/Akt pathway, and the apoptosis-inducing potential of EEZS was promoted in the presence of PI3K/Akt inhibitor. In addition, EEZS enhanced the production of ROS, whereas N-acetyl cysteine (NAC), a ROS scavenger, markedly suppressed growth inhibition and inactivation of the PI3K/Akt signaling pathway induced by EEZS. Furthermore, NAC significantly attenuated the EEZS-induced apoptosis and reduction of cell viability. CONCLUSIONS: Taken together, our results indicate that exposure to EEZS exhibits anti-cancer activity in T24 bladder cancer cells through ROS-dependent induction of apoptosis and inactivation of the PI3K/Akt signaling pathway.