• The Journal of Korean Obstetrics and Gynecology
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• v.23 no.2
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• pp.38-56
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• 2010

Purpose: This study was designed to evaluate the effect of administration of Foeniculi Fructus on ovarian functions and differential gene expressions related cell viability such as caspase-3, MAPK and MPG in female mice. Methods: We administered the Foeniculi Fructus to 6-week-old female CF-1 mice for 4, 8, 12 days. After administration of Foeniculi Fructus with 0.1, 1, 10, $100\;mg/m{\ell}$ concentration in the comparison of control group with $0\;mg/m{\ell}$, we observed the mean number of total ovulated oocytes and the number of morphologically normal oocytes. After entosomatic fertilization, we observed the rate of fertilized 2-cell embryos to blastocyst stage in vitro. Also we chose the caspase-3 for cell apoptosis, MAPK and MPG genes for cell viability and DNA repair by RT-PCR. Results: 1. In case of 4, 8, 12day administration of Foeniculi Fructus with 0.1, 1, 10, $100\;mg/m{\ell}$, the mean number of total ovulated oocytes and the number of morphologically normal oocytes were increased in the comparison of control group. 2. In case of 4, 8, 12day administration of Foeniculi Fructus with 0.1, 1, 10, $100\;mg/m{\ell}$, the rates of blastocyst formation from 2-cell stages were increased in the comparison of control group. 3. In case of 4, 8, 12day administration of Foeniculi Fructus with 0.1, 1, 10, $100\;mg/m{\ell}$, the gene expression of caspase-3, MAPK, MPG didn't show significant result in the comparison of control group. Conclusion: This study shows that Foeniculi Fructus has significant effects on the increase of the function on ovulation and embryonic development of female mice. But this results have nothing to do with caspase-3, MAPK and MPG genes. So we need a further study for which genes are related to the activation of reproductive functions of Foeniculi Fructus.

• Journal of Life Science
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• v.23 no.4
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• pp.518-528
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• 2013

Scutellaria baicalensis, belonging to the family Labiatae, is widely distributed in Korea, China, Mongolia, and eastern Siberia. It has been used in traditional medicine for various diseases, such as dysentery, pyrexia, jaundice, and carbuncles. In addition, S. baicalensis is reported to possess various beneficial pharmacological activities, including anti-inflammatory, antidiabetic, antiviral, antihypertension, antioxidant, and anticancer effects. However, the molecular mechanisms of its anticancer activity have not been clearly elucidated. In the present study, we investigated the proapoptotic effects of ethanol extract of S. baicalensis (EESB) on human renal cell carcinoma Caki-1 cells. The anti-proliferative activity of EESB was associated with apoptosis induction, which was associated with the up-regulation of death receptor 4, the Fas ligand, and Bax and the down-regulation of Bid, XIAP, and cIAP-1 proteins. EESB treatment also induced mitochondrial dysfunction, proteolytic activation of caspase-3, -8, and -9 and degradation of caspase-3 substrate proteins, such as poly (ADP-ribose) polymerase, ${\beta}$-catenin, and phospholipase C-${\gamma}1$. However, pretreatment of a pan-caspase inhibitor, z-VAD-fmk, significantly attenuated the EESB-induced apoptosis. Taken together, these findings suggest that EESB may be a potential chemotherapeutic agent. Further studies will be needed to identify the active compounds that confer the anticancer activity of S. baicalensis.

• Journal of Life Science
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• v.31 no.4
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• pp.400-409
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• 2021

Sanguinarine, a natural benzophenanthridine alkaloid, has been considered a potential therapeutic target for the treatment of cancer because it can induce apoptosis in human cancer cells; however, the underlying mechanisms of action still remain unclear. Tumor suppressor p53 deletion or mutation is an important reason for the resistance of colorectal cancer cells to anticancer agents. Therefore, in the present study, the role of p53 during apoptosis induced by sanguinarine was investigated in p53wild type (WT, p53+/+) and p53null (p53+/+) HCT116 colon carcinoma cells. Sanguinarine significantly caused greater reductions in cell viability in HCT116 (p53+/+) cells than in HCT116 (p53-/-) cells. Consistently, sanguinarine promoted more DNA damage and apoptosis in HCT116 (p53+/+) cells than in HCT116 (p53-/-) cells while increasing the expression of p53 and cyclin-dependent kinase inhibitor p21^WAF1/CIP1. Sanguinarine increased the activity of caspase-8 and caspase-9, which are involved in the initiation of extrinsic and intrinsic apoptosis pathways, respectively, and it activated caspase-3, a typical effect caspase, in HCT116 (p53+/+) cells. Sanguinarine also increased the generation of reactive oxygen species (ROS), and the Bax/Bcl-2 ratio, while destroying the integrity of mitochondria in HCT116 (p53+/+) cells, but not in HCT116 (p53-/-) cells. Overall, the results indicate that sanguinarine induced p53-dependent apoptosis through ROS-mediated activation of extrinsic and intrinsic apoptotic pathways in HCT116 colorectal cancer cells.

• Journal of Gastric Cancer
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• v.3 no.1
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• pp.38-43
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• 2003

Purpose: Caspase 2, a member of the family of ICE-like proteases, is activated by the Fas pathway and induces apoptosis by triggering the caspase cascade. The purpose of this study was to determine whether the expression pattern of caspase 2 might be associated with gastric cancer development and if so, to determine to which pathologic parameter it is linked. Materials and Methods: For the construction of the gastric cancer tissue microarray, 78 paraffin-embedded tissues containing gastric cancer areas were cored 3 times and transferred to the recipient master block. The expression pattern of caspase 2 was examined on tissue microarray slides by using immunohistochemistry and was compared with pathologic parameters, including histologic type, depth of invasion, lymph node metastasis, and peritoneal dissemination. Results: Caspase 2 was expressed on superficial and foveolar epithelial cells and lymphocytes in the gastric mucosa, mainly in cytoplasm. We found loss of caspase 2 expression in 41 ($52.6\%$) of the 78 gastric cancer tissues. Statistically, histologic type and other pathologic parameters were not related with loss of caspase 2 expression Conclusion: Our findings provide enough evidence that loss of caspase 2 expression may contribute to the development of Korean gastric cancer and that it might be one of the possible escape mechanisms from apoptosis in gastric cancer.

• The Korea Journal of Herbology
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• v.22 no.2
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• pp.35-43
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• 2007

Objectives : The purpose of this study was to investigate the effect of Bo-du-san (BOS) on apoptosis in human gastric cancer cells, SNU-l cells. BOS, a drug preparation consisting of two herbs, that is, Crotonis Fructus (Strychni ignatii Semen, bodu in Korean) and Glycyrrhizae Radix (Glycyrrhizae uralensis FISCH, Gamcho in Korean). Methodss : In this study, methanol extract of BOS was examined for cytotoxic activity on human gastric cancer cells, SNU-1 cells, using XTT assay, with an IC50 value was 0.7 mg/ml and 0.3 mg/ml at 24 hrs and 48 hrs, respectively. Apoptosis induction by BDS in SNU-l cells was verified by the induction of DNA fragmentation, cleavage of poly ADP-ribose polymerase (PARP), and activation of caspase-3, -8 and -9. Inhibitors of caspase-3, -8 and -9 (Ac-DEVD-CHO, Z-IETD-FMK and Z-LEHD-FMK) efficiently blocked BOS-induced cell death of SNU-l. Resultss : BOS-induced cell death was via caspase dependent apoptosis. Moreover, treatment of BOS result in the decrease the G1/S cycle regulation proteins (cyclin D1 and E) expression and increase CDK inhibitor proteins (p21 and p27) expression, and increase apoptotic protein, p53 expression. Thus, BOS induces apoptosis in SNU-1 cells via cell cycle arrested in G1 phase. Conclusions : These results indicated that BOS has some potential for use as an anti-cancer agent.

• The Korean Journal of Physiology and Pharmacology
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• v.7 no.4
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• pp.199-205
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• 2003

Osteoblasts are affected by TNF-${\alpha}$ overproduction by immune cells during inflammation. It has been suggested that functional $NF-{\kappa}B$ sites are involved in TNF-${\alpha}$-induced bone resorption. Thus, we explored the effect of pyrrolidine dithiocarbamate (PDTC), which potently blocks the activation of nuclear factor $(NF-{\kappa}B)$, on the induction of TNF-${\alpha}$-induced activation of JNK/SAPK, AP-1, cytochrome c, caspase and apoptosis in MC3T3E1 osteoblasts. Pretreatment of the cells with PDTC blocked TNF-${\alpha}$-induced $NF-{\kappa}B$ activation. TNF-${\alpha}$-induced activation of AP-1, another nuclear transcription factor, was suppressed by PDTC. The activation of c-Jun N-terminal kinase, implicated in the regulation of AP-1, was also down regulated by PDTC. TNF-${\alpha}$-induced apoptosis, release of cytochrome c and subsequent activation of caspase-3 were abolished by PDTC. TNF-${\alpha}$-induced apoptosis was partially blocked by Ac-DEVD-CHO, a caspase-3 inhibitor, suggesting that caspase-3 is involved in TNF-${\alpha}$-mediated signaling through $NF-{\kappa}B$ in MC3T3E1 osteoblasts. Thus, these results demonstrate that PDTC, has an inhibitory effect on TNF-${\alpha}$-mediated activation of JNK/SAPK, AP-1, cytochrome c release and subsequent caspase-3, leading to the inhibition of apoptosis. Our study may contribute to the treatment of TNF-${\alpha}$-associated immune and inflammatory diseases such as rheumatoid arthritis and periodontal diseases.

• Journal of Life Science
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• v.18 no.11
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• pp.1499-1506
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• 2008

To examine antitumor activity of the edible plant Zanthoxylum schinifolium, the cytotoxic effect of various organic solvent extracts of its stems on human acute leukemia Jurkat T cells was investigated. Among these extracts such as methanol extract (SS-7), methylene chloride extract (SS-8), ethyl acetate extract (SS-9), n-butanol extract (SS-10), and residual fraction (SL-11), SS-8 exhibited the most cytotoxic activity against Jurkat T cells. The methylene chloride extract (SS-8) possessed the apoptogenic activity capable of inducing sub-G1 peak along with apoptotic DNA fragmentation in Jurkat T cells. Western blot analysis revealed that SS-8 induced apoptosis via mitochondrial cytochrome c release into cytoplasm, subsequent activation of caspase-9 and caspase-3, and cleavage of PARP, which could be blocked by overexpression of Bcl-xL. Jurkat T cell clone I2.1 $FADD^{-/-}$) and Jurkat T cell clone I9.2 (caspase-$8^{-/-}$ were as sensitive as was the wild-type Jurkat T cell clone A3 to the cytotoxic effect of SS-8, suggesting no contribution of Fas/FasL system to the SS-8-mediated apoptosis. The GC-MS analysis of SS-8 showed that it was composed of 16 ingredients including 9,12-octadecanoic acid (18.62%), 2,4-dihydro-5-methyl-4- (1-methylethylidene)- 2-(4-nitrophenyl)-3H- pyrazol-3-one (14.97%), hexadecanoic acid (14.23%), (z,z)-6,9-pentadecadien- 1-ol (13.73%), 5,6-dimethoxy-2-methyl benzofuran (10.95%), and 4-methoxy-2-methylcinnamic acid (5.38%). These results demonstrate that the methylene chloride extract of the stems of Z. schinifolium can induce apoptotic cell death in Jurkat T cells via intrinsic mitochondria-dependent caspase cascade regulated by Bcl-xL without involvement of the Fas/FasL system.

• Korean Journal of Plant Resources
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• v.32 no.6
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• pp.669-676
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• 2019

Zanthoxylum piperitum D.C. (ZP) peels has been used as a natural spice and herb medicine for hypertension reduction, for strokes, and for its anti-bacterial and anti-oxidant activity. However, the anti-inflammatory mechanisms employed by ZP have yet to be completely understood. In this study, we elucidate the anti-inflammatory mechanism of ZP in lipopolysaccharide (LPS)-induced RAW264.7 cells. We evaluated the effects of ZP in LPS-induced levels of inflammatory cytokines, prostaglandin E₂ (PGE₂), and caspase-1 using ELISA. The expression levels of inflammatory-related genes, including cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS), were assayed by Western blot analysis. We elucidated the effect of ZP on nuclear factor (NF)-κB activation by means of a luciferase activity assay. The findings of this study demonstrated that ZP inhibited the production of inflammatory cytokine and PGE₂ and inhibited the increased levels of COX-2 and iNOS caused by LPS. Additionally, we showed that the anti-inflammatory effect of ZP arises by suppressing the activation of NF-κB and caspase-1 in LPS- induced RAW264.7 cells. These results provide novel insights into the pharmacological actions of ZP as a potential candidate for development of new drugs to treat inflammatory diseases.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.1
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• pp.224-229
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• 2005

Ginseng radix, the root of Panax ginseng C.A.Meyer (Araliaceae), has traditionally been used for the treatment of various disorders including cerebrovascular accident (CVA). In the present study, the effect of Ginseng radix on c-Fos expression and apoptosis in the hippocampal CA1 region of gerbils following transient global ischemia was investigated via immunohistochemistry for c-Fos and caspase-3 and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. Enhanced c-Fos-, TUNEL-, and caspase-3-positivities were detected in the hippocampal CA1 region in ischemic gerbils. Administration of the aqueous extract of Ginseng radix suppressed this ischemia-induced increment in the numbers of c-Fos-, TUNEL-, and caspase-3-positive cells. These results suggest that Ginseng radix has an inhibitive effect on the induction of c-Fos expression and apoptosis seen following transient global ischemia.

• The Journal of Korean Medicine
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• v.36 no.4
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• pp.19-34
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• 2015

Objectives: This study was performed to investigate the anti-tumor effect of O. japonicus extracts on intrahepatic cholangiocarcinoma cell line SNU-1079. Methods: Cholangiocarcinoma SNU-1079 cells were treated with various concentrations of O. japonicus DW and EtOH extracts ($0-300{\mu}g/ml$) for 24, 48 or 72 h. Cell viability was evaluated through a PMS/MTS assay, and the apoptosis rate was examined through ELISA assay and flow cytometry analysis. The mRNA expression of apoptosis- and cell cycle progression-related genes (Bcl-2, Mcl-1, Bax, Survivin, Cyclin D1, and p21) was evaluated using real-time PCR, and the caspase activity was examined using immunoblot analysis. Results: O. japonicus extracts inhibited cell proliferation and increased apoptosis rate in both ELISA assay and flow cytometry analysis. O. japonicus extracts decreased Bcl-2, Mcl-1, Survivin, and Cyclin D1 mRNA expression and increased Bax mRNA level. O. japonicus extracts also increased Caspase-3 activation. Overall, O. japonicus DW extracts were more effective than EtOH extracts. Conclusions: O. japonicus inhibited cell proliferation and induced apoptosis in SNU-1079 cells via mitochondria -mediated intrinsic pathway, which leads to Caspase-3 activation. The results indicate that O. japonicus is a potential therapeutic herb with anti-tumor effect against intrahepatic cholangiocarcinoma.