• Food Science and Preservation
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• v.31 no.2
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• pp.276-286
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• 2024

In the present study, we investigated whether a mixture of fucoidan and Crepidiastrum denticulatum extract (FCE) had the potential to improve the therapeutic efficacy of cancer treatment. The results demonstrated that FCE significantly reduced cell viability and induced the release of LDH (lactate dehydrogenase) and DNA fragmentation in HepG2 cells in a dose-dependent manner. In addition, FCE treatment also increased the protein expression level of p53, the release of cytochrome c, and the loss of mitochondrial membrane potential. Moreover, FCE dose-dependently increased protein expression levels of Bax, and cleaved caspase-3 and -9. However, FCE decreased the protein expression level of Bcl-2. These results suggest that FCE inhibits cell proliferation and induces apoptosis via the mitochondrial-mediated intrinsic pathway. The present study demonstrates that FCE can be used as an anti-cancer agent for liver cancer based on apoptosis mechanism.

• Journal of Embryo Transfer
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• v.32 no.4
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• pp.275-285
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• 2017

Lysophosphatidic acid (LPA) is an important signaling molecule. Here, the effect and mechanism of LPA on the preimplantation development of porcine embryos during in vitro culture (IVC) was examined. Porcine embryos were cultured in porcine zygote medium (PZM-3) supplemented with $30{\mu}M$ LPA during different days. There was a significantly higher cleavage rate in Day 1-7 and significantly higher total cell number of blastocysts in Day 1-3 and Day 4-7. It was also found that messenger RNA (mRNA) expression level of PCNA, BCL2 and BAX in blastocysts obtained from D1-7 group were significantly higher and BCL2/BAX mRNA ratio in D1-3 group was significantly lower than control group but Day 4-7 and Day 1-7 groups were comparable with control group. Treatment with $20{\mu}M$ PLC inhibitor significantly decreased the embryo cleavage rate and blastocyst formation rate. Moreover, LPA as an activator of PLCs, enhanced the $30{\mu}M$ LPA + $20{\mu}M$ U73122 group embryo cleavage rate which similar with control group. In conclusion, the results suggest that treatment with LPA during IVC improves the porcine early embryo cleavage by activation of PLC signaling pathway and regulate the mRNA expression that contribute to total cell number of blastocysts during blastocyst formation.

• The Korean Journal of Physiology and Pharmacology
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• v.23 no.1
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• pp.21-28
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• 2019

Swertiamarin (STM) is an iridoid compound that is present in the Gentianaceae swertia genus. Here we investigated antiapoptotic effects of STM on carbon tetrachloride ($CCl_4$)-induced liver injury and its possible mechanisms. Adult male Sprague Dawley rats were randomly divided into a control group, an STM 200 mg/kg group, a $CCl_4$ group, a $CCl_4+STM$ 100 mg/kg group, and a $CCl_4+STM$ 200 mg/kg group. Rats in experimental groups were subcutaneously injected with 40% $CCl_4$ twice weekly for 8 weeks. STM (100 and 200 mg/kg per day) was orally given to experimental rats by gavage for 8 consecutive weeks. Hepatocyte apoptosis was determined by TUNEL assay and the expression levels of Bcl-2, Bax, and cleaved caspase-3 proteins were evaluated by western blot analysis. The expression of $TGF-{\beta}1$, collagen I, collagen III, CTGF and fibronectin mRNA were estimated by qRT-PCR. The results showed that STM significantly reduced the number of TUNEL-positive cells compared with the $CCl_4$ group. The levels of Bax and cleaved caspase-3 proteins, and $TGF-{\beta}1$, collagen I, collagen III, CTGF, and fibronectin mRNA were significantly reduced by STM compared with the $CCl_4$ group. In addition, STM markedly abrogated the repression of Bcl-2 by $CCl_4$. STM also attenuated the activation of the PI3K/Akt pathway in the liver. These results suggested that STM ameliorated $CCl_4$-induced hepatocyte apoptosis in rats.

• Herbal Formula Science
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• v.24 no.4
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• pp.311-321
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• 2016

Chronic or acute alcohol abuse often leads to liver injury associated with alcoholic hepatitis, liver fibrosis, cirrhosis, and liver cancer. In addition to the liver, alcohol abuse also induces a variety of other tissue injuries including pancreatitis, cardiomyopathy, neurotoxicity and muscle loss. Chronic skeletal muscle myopathy, independent of peripheral neuropathy, is well recognised in alcoholic patients. Several mechanisms may be involved in the pathogenesis of alcoholic myopathy. Ethanol is a potent inhibitor of muscle protein synthesis. Gastrocnemius and plantaris muscles are Type II fiber-predominant and usually considered representative of the musculature as a whole. Whereas, soleus muscle is Type I fiber predominant. Shihosogan-san is a traditional Korean medicine that is widely employed to treat indigestion and liver diseases. Muscle diseases are often related to liver diseases and conditions. We therefore tested the hypothesis that treatment with Shihosogan-san could ameliorate the ethanol-induced changes in muscle protein synthesis. Young male Sprague-Dawley rats were orally given 25% ethanol (5ml/kg, body weight) daily with Ethanol for 28 days. Normal group was similarly administrated with saline. In Shihosogan-san treated group, rats were orally administrated Shihosogan-san extract, and rats of EtOH group were given with the vehicle only. After 4 week, the morphology of gastrocnemius and plantaris muscles were assessed by hematoxylin and eosin staining. For comparative purposes, liver function was also investigated. The muscles from rats of EtOH group displayed a significant reduction in average cross section area compared to Normal group. Shihosogan-san treated group had increased fiber compared to the EtOH group. Moreover, Shihosogan-san treated group compared with EtOH group showed significantly decreased pro-apoptotic BAX expression and increased anti-apoptotic Bcl-2 expression. In conclusion, Shihosogan-san extract showed ameliorating effects on chronic alcohol toxicity in skeletal muscle.

• Biomolecules & Therapeutics
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• v.19 no.1
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• pp.21-26
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• 2011

Ceramide is an important lipid mediator of extracellular signals that control various cellular functions, including apoptosis. In this study, we showed that ceramide induced apoptosis in U373MG human glioblastoma cells associated with G1 cell cycle arrest. Treatment of cells with ceramide increased proapoptotic Bax expression and inhibited the expression of antiapoptotic Bcl-2 and Bcl-xL Ceramide also downregulated cyclin E, cyclin D1, cdk 2, and cdk4 which are involved in regulating cell cycle. In addition, ceramide suppressed phosphorylation of Akt, Bad, p70 S6 kinase, and 4E-BP1, suggesting the involvement of Akt/mTOR signaling pathway. Additionally, okadaic acid, an inhibitor of protein phosphatase 2A, partially blocked the ceramide mediated inhibition of phosphorylation of Akt and 4E-BP1. These results suggest that ceramide induces apoptosis in U373MG glioblastoma cells by regulating multiple signaling pathways that involve cell cycle arrest associated with Akt signaling pathway.

• Korean Journal of Plant Resources
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• v.31 no.3
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• pp.268-273
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• 2018

Hepatic ischemia-reperfusion injury (HIRI) is linked with high mortality rate. Several agents have been developed so far to reduce the risk of HIRI. In this study, we investigated the effects of combined treatment of Ginko biloba leaves extract and vitamin C (GLEVC) on hepatic ischemia-reperfusion injury. To explore the protective effects of GLEVC on HIRI rats model were tested. After the development of HIRI by using clamping method rats were then randomly divided into four groups. Different doses of GLEVC were administered in HIRI rat model. The level of ALT, AST, SOD and MDA content in serum were detected in HIRI groups. Moreover, the activity of SOD, content of MDA, and GSH in hepatic tissue were also examined. Bcl-2 and Bax protein expression were detected by immunohistochemical staining method. Compared with sham group, GLEVC has the protective effect on the HIRI-induced model. Level of ALT, AST, and MDA in blood were significantly lower in GLEVC group compared with HIRI-induced group. Moreover, SOD activity and GSH were increased in GLEVC group whereas MDA content was reduced by GLEVC treatment. Furthermore, HIRI-induced Bax protein was reduced upon GLEVC treatment, whereas Bcl-2 protein expression was enhanced. These results demonstrate that GLEVC treatment may provide potential ameliorative therapy by reducing damaged signaling mechanism in hepatic ischemia/reperfusion injury model.

• Journal of Pharmaceutical Investigation
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• v.37 no.5
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• pp.287-290
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• 2007

Intrinsic or acquired resistance to chemotherapeutic drugs is one of the major obstacles to effective cancer treatment. Hypoxia is widespread in solid tumors as a consequence of decreased blood flow in the tumor-derived neovasculature. The recent finding of a link between hypoxia and chemoresistance prompted us to investigate whether hypoxia induces doxorubicin resistance in human MCF-7 breast cancer cells. Low oxygen concentration decreased the doxorubicin sensitivity in MCF-7 cells. The expression of p-glycoprotein, a major MDR-related transporter, and those of apoptosis-related proteins (anti-apoptotic Bcl-2, Bcl-XL and pro-apoptotic Bax) were not altered by hypoxia in MCF-7 cells. Intracellular uptake of doxorubicin was significantly decreased under hypoxic conditions. Decreased cellular uptake of doxorubicin under hypoxia may contribute to causing doxorubicin resistance in these cells. The use of agents that can modulate the doxorubicin uptake for adjuvant therapy may contribute to improving the therapeutic efficacy of doxorubicin in breast cancer patients.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.11
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• pp.1589-1594
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• 2016

Piperine [(E,E)-5-(3,4-methtylenedioxyphenyl)-2,4-pentadienolypiperidide] is a principal of Piperaceae, including Piper nigrum L. and Piper longum Linn., which has been used as a spice and traditional medicine. In this study, we investigated whether or not piperine has anti-cancer effects on AGS human gastric cancer cells. The results demonstrated that piperine not only inhibited proliferation using MTT assay but also induced apoptotic bodies using DAPI assay in a dose-dependent manner in response to piperine. Expression levels of p53, Bax (pro-apoptotic), cleaved caspase-9, and cleaved-PARP increased, whereas expression levels of Bcl-2, XIAP (anti-apoptotic), and Akt decreased in a dose-dependent manner compared with the control by western blotting analysis. To identify the connection between phospo-Akt and Bcl-2 family in response to piperine, LY249002 (Akt inhibitor) was treated with piperine ($150{\mu}M$). The results were shown that expression of phospo-Akt was reduced whereas expression of Bax and cleaved-PARP increased in a dose-dependent manner. These results indicate that piperine induced apoptosis in AGS cells and may serve as a chemopreventive or therapeutic agent for human gastric cancer.

• Clinical and Experimental Pediatrics
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• v.51 no.3
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• pp.307-314
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• 2008

Purpose : Capsaicin, the major pungent ingredient in red pepper, has long been used in spices and food additives. It has been recently shown to induce apoptosis in several cell lines through a not well known mechanism. The aim of this study was to investigate the apoptosis-inducing effect of capsaicin on gastric cancer cells, and to provide valuable information concerning the application of capsaicin for therapeutic purposes. Methods : Cultured SNU-668 cells were treated with capsaicin. We analyzed cell survival by trypan blue and crystal violet analysis, cell cytotoxicity by MTT assay, apoptosis by nuclear condensation and DNA fragmentation, bcl-2 and bax mRNA expression by RT-PCR, and the expression of apoptosis related proteins by Western immunoblot analysis. In order to assess whether the growth inhibitory effect of anticancer drugs is enhanced by capsaicin, we investigated the effects of cell cytotoxicity and the expression of apoptosis related proteins of etoposide and adriamycin treated with capsaicin in cells. Results : Capsaicin inhibited growth of SNU-668 cells in a dose-dependent manner. This inhibitory effect of capsaicin on cell growth was mainly due to the induction of apoptosis as evidenced by DNA fragmentation, nuclear condensation and the expression of apoptosis related proteins. Furthermore, capsaicin prominently reduced the ratio of anti-apoptotic Bcl-2 to pro-apoptotic Bax and consequently increased caspase-3 activity. The cells treated with capsaicin were more sensitive to death induced by etoposide and adriamycin than the cells without capsaicin. Conclusion : These results demonstrate that capsaicin efficiently induced apoptosis in SNU-668 cells through a caspase-3-dependent mechanism and sensitizes cancer cells to anticancer drugs toward apoptotic cell death, which may contribute to its anticancer effect and chemosensitizer function against gastric cancer.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.4
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• pp.955-959
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• 2005

We previously demonstrated that the methylene chloride fraction of Scutellaria barbata suppessed human leukemic U937 cell proliferation by inducing apoptosis. In the present study, we have isolated luteolin from Scutellaria barbata and evaluated its apoptotic mechanism in Lewis lung carcinoma cells. Luteolin inhibited the proliferation of Lewis lung carcinoma cells in a concentration-dependent manner. Luteolin effectively increased the portion of $sub-G_1$ DNA content (apoptotic portion) and apoptotic Annexin-V positive cells in a concentration-dependent manner by FACS analysis. Caspase 9 and caspase 3 were activated and PARP was effectively cleaved by luteolin. It also increased the ratio of Bax to Bcl-2 through the decrease of Bcl-2 expression by Western blotting and reduced mitochondrial membrane potential following TMRE staining. These results suggest that luteolin can induce apoptosis through the mitochondrial mediated pathway.