• Asian Pacific Journal of Cancer Prevention
• /
• 제16권18호
• /
• pp.8135-8140
• /
• 2016

Background: Cell cycle regulatory proteins are suitable targets for cancer therapeutic development since genetic alterations in many cancers also affect the functions of these molecules. Strobilanthes crispus (S. crispus) is traditionally known for its potential benefits in treating various ailments. We recently reported that an active sub-fraction of S. crispus leaves (SCS) caused caspase-dependent apoptosis of human breast cancer MCF-7 and MDA-MB-231 cells. Materials and Methods: Considering the ability of SCS to also promote the activity of the antiestrogen, tamoxifen, we further examined the effect of SCS in modulating cell cycle progression and related proteins in MCF-7 and MDA-MB-231 cells alone and in combination with tamoxifen. Expression of cell cycle-related transcripts was analysed based on a previous microarray dataset. Results: SCS significantly caused G1 arrest of both types of cells, similar to tamoxifen and this was associated with modulation of cyclin D1, p21 and p53. In combination with tamoxifen, the anticancer effects involved downregulation of $ER{\alpha}$ protein in MCF-7 cells but appeared independent of an ER-mediated mechanism in MDA-MB-231 cells. Microarray data analysis confirmed the clinical relevance of the proteins studied. Conclusions: The current data suggest that SCS growth inhibitory effects are similar to that of the antiestrogen, tamoxifen, further supporting the previously demonstrated cytotoxic and apoptotic actions of both agents.

• Asian Pacific Journal of Cancer Prevention
• /
• 제16권17호
• /
• pp.7943-7957
• /
• 2015

Background and Aims: Colorectal cancer is one of the leading causes of death in the world. The aim of this study was to investigate the growth-suppression potentiality of a crude saponin extract (CSENS) prepared from medicinal herb, Nigella sativa, on human colon cancer cells, HCT116. Materials and Methods: HCT116 cells were subjected to increasing doses of CSENS for 24, 48 and 72 h, and then harvested and assayed for cell viability by WST-1. Flow cytometry analyses, cell death detection ELISA, fluorescent stains (Hoechst 33342 and acridine orange/ethidium bromide), DNA laddering and comet assays were carried out to confirm the apoptogenic effects of CSENS. Luciferase reporter gene assays, quantitative reverse transcription-polymerase chain reaction and Western blot analyses were performed to assess the impact of CAERS and CFEZO on the expression levels of key regulatory proteins in HCT116 cells. Results: The results demonstrated that CSENS inhibited proliferation and induced apoptosis. Apoptosis was confirmed by flow cytometry analyses, while CSENS-treated cells exhibited morphological hallmarks of apoptosis including cell shrinkage, irregularity in cellular shape, cellular detachment and chromatin condensation. Biochemical signs of apoptosis, such as DNA degradation, were observed by comet assay and gel electrophoresis. The pro-apoptotic effect of CSENS was caspase-3-independent and associated with increase of the Bax/Bcl-2 ratio. CSENS treatment down-regulated transcriptional and DNA-binding activities of NF-${\kappa}B$ and AP-1 proteins, associated with down-regulation of their target oncogenes, c-Myc, cyclin D1 and survivin. On the other hand, CSENS up-regulated transcriptional and DNA-binding activities of Nrf2 and expression of cytoprotective genes. In addition, CSENS modulated the expression levels of ERK1/2 MAPK, p53 and p21. Conclusions: These findings suggest that CSENS may be a valuable agent for treatment of colon cancer.

• 약학회지
• /
• 제55권4호
• /
• pp.301-308
• /
• 2011

Diabetes has been one of major health risks in industrialized countries. AMP-activated protein kinase (AMPK) has been focused as a novel therapeutic target for the treatment of metabolic syndromes, because AMPK increases glucose uptake through independent insulin signal pathway. In this study, we investigated the anti-diabetic effect of Angelica gigas Nakai extract (AGNEX), a mixture of decursin and decursinol angelate (53 : 47), decursin and decursinol angelate on blood glucose, glucose transport (GLUT) and AMPK expression levels in streptozotocin (STZ)-induced diabetic rats. To induce diabetes, 50 mg/kg of STZ was injected via i.v. route and AGNEX 2 mg/kg (STZ+AG), decursin 2 mg/kg (STZ+D), decursinol angelate 2 mg/kg (STZ+DA), and metformin 100 mg/kg (STZ+M) were administered orally for 21 days. STZ+DA group showed a significant decrease in fasting blood glucose levels compared to the other groups. Decursinol angelate significantly upregulated expression of glucose transporter 4 (GLUT4) and phosphorylation of AMPK (p-AMPK) in skeletal muscle of rats. In pancreas of rats, decursinol angelate significantly increased expression of GLUT2 through down-regulation of p-AMPK. In addition to the result of pancreatic islets morphology, AGNEX, decursin, decursinol angelate, and metformin treated group recovered ${\beta}$-cell damage by hyperglycemia. These results indicate that decursinol angelate might be a potential anti-diabetic agent and AGNEX could be useful in the treatment of diabetes mellitus.

• 동의생리병리학회지
• /
• 제20권4호
• /
• pp.966-972
• /
• 2006

The effect of water extract of Chungjogupae-tang (CJGPT) was investigated _on the growth of human lung carcinoma A549 cells. Methods: MTT assay and fluorescent microscope peformed to compare and examine the efficacy of CJGPT treatment on the cytostaticity of lung cancer cells in proportion to time and doses, and DAPI staining and Western blot analysis were used to examine their effect on apoptosis. In addition, the quantitative RT-PCR was used to examine to lung cancer cells growth, and Prostaglandin E2 activity were measured. Results: Exposure of A549 cells to CJGPT respited in the growth inhibition and apoptosis in a dose-dependent manner as measured by MTT assay and fluorescent microscope. The antiproliferative effect by CJGPT treatment in A549 cells was associated with morphological changes such as membrane shrinking and cell rounding up. CJGPT treatment resulted in an up-regulation of cyclin-dependent kinase inhibitor p21 (WAFl/CIPl) in a p53-independent fashion. We found that CJGPT treatment decreased the levels of cyclooxygenase (COX)-2 and inducible nitric oxide synthease (iNOS) expression without significant changes in the expression of COX-1 , which was correlated with a decrease in prostaglandin E2 (PGE2) synthesis. Conclusion: These findings suggested that CJGPT-induced inhibition of human lung carcinoma A549 cell growth was connected with the induction of apoptotic cell death and the results provided important new insights into the possible molecular mechanisms of the anti-cancer activity of CJGPT.

• Archives of Pharmacal Research
• /
• 제27권1호
• /
• pp.68-76
• /
• 2004

Mistletoe lectin has been reported to induce apoptosis in different cancer cell lines in vitro and to show antitumor activity against a variety of tumors in animal models. We previously demonstrated the Korean mistletoe lectin (Viscum album var. coloratum, VCA)-induced apoptosis by down-regulation of Bcl-2 and telomerase activity and by up-regulation of Bax through p53- and p21-independent pathway in hepatoma cells. In the present study, we observed the induction of apoptotic cell death through activation of caspase-3 and the inhibition of telomerase activity through transcriptional down-regulation of hTERT in the VCA-treated A253 cells. We also observed the inhibition of telomerase activity and induction of apoptosis resulted from dephosphorylation of Akt in the survival signaling pathways. In addition, combining VCA with the inhibitors of phosphatidylinositol 3-kinase (PI3-kinase) upstream of Akt, wortmannin and LY294002 showed an additive inhibitory effect of telomerase activity. In contrast, the inhibitor of protein phosphatase 2A (PP2A), okadaic acid inhibited VCA-induced dephosphorylation of Akt and inhibition of telomerase activity. Taken together, VCA induces apoptotic cell death through Akt signaling pathway in correlated with the inhibition of telomerase activity and the activation of caspase-3. From these results, together with our previous studies, we suggest that VCA triggers molecular changes that resulting in the inhibition of cell growth and the induction of apoptotic cell death of cancer cells, which suggest that VCA may be useful as chemotherapeutic agent for cancer cells.

• 생명과학회지
• /
• 제21권1호
• /
• pp.9-14
• /
• 2011

심박수(heart rate) 및 산소 소비량(oxygen consumption) 등의 생리학적 변수는 운동자각도(RPE)와 밀접한 관련이 있으며, RPE의 남녀차이에 의한 예측 운동강도의 정확성은 아직 밝혀지지 않고 있고, 본 연구는 남녀 대학생의 심장 혈관 및 신진대사의 반응을 평가하고 남녀의 차이를 밝히는 데 있다. 남자대학생($25.1{\pm}1.56$ yr)과 여자대학생($25.0{\pm}4.12$ yr) 각각 10명이 본 연구에 자발적으로 참여를 하였고, 본 연구를 위하여 설정된RPE는 Borg의 15 범주에서 결정을 하였으며, 점증적 운동부하(graded exercise testing)는 Bruce Treadmill Protocol을 이용하였다. 남녀의 평균 slope (p=0.501)와 RPE의 plotting rates와 최대산소섭취율(% $VO_2$max)은 유의한 차이가 나타나지 않았다. 각자의 상대적 최대산소섭취량은 남학생의 경우52.36${\pm}$7.35 ml/kg/min, 여학생은 41.44${\pm}$6.71 ml/kg/min로 나타나 두 그룹간에 유의하게 큰 차이가 있었으며, 절대적 최대산소섭취량은 남학생은 4.05${\pm}$0.36 l/min, 여학생은 2.53${\pm}$0.39 l/min로 나타나 두 그룹간에 큰 차이가 나타냈다. 남학생과 여학생간의 slope, y-intercept, SEE는 통계적으로 유의한 차이는 없었다. 본 연구에서 운동강도에 따른 남학생과 여학생의 RPE 의 차이는 유의하게 나타나지 않았다. 이상의 결과로 보아 RPE는 운동중 산소섭취량에 대한 운동강도의 예측에 남녀별 차이가 없어 유효한 예측인자라고 사료된다.

• Korean Journal of Radiology
• /
• 제23권5호
• /
• pp.548-554
• /
• 2022

Objective: To evaluate the safety and feasibility of prostatic artery embolization (PAE) via transradial access (TRA) compared with transfemoral access (TFA). Materials and Methods: This retrospective study included 53 consecutive men with lower urinary tract symptoms (LUTS) who underwent PAE between September 2018 and September 2021. Thirty-one patients (mean age ± standard deviation: 70.6 ± 8.4 years) were treated with TFA, including 14 patients treated before adopting TRA. Since December 2019, TRA has also been attempted with the procedure's selection criteria of patent carpal circulation and a height ≤ 172 cm, with 22 patients treated via TRA (69.1 ± 9.6 years). Parameters of technical success (defined as successful bilateral embolization), clinical success (defined as LUTS improvement), procedural time, radiation dose, and adverse events were compared between the two groups using the Fisher's exact test, independent sample t test, Wilcoxon signed-rank test, or Mann-Whitney test. Results: All patients received at least one-side PAE. Technical success of PAE was achieved in most patients (TRA, 21/22; TFA, 30/31; p > 0.999). No technical problem-related conversion from TRA to TFA occurred. The clinical success rate was 85% (11/13) in patients with TRA, and 89% (16/18) in patients with TFA for follow-up > 2 weeks post-PAE (median, 3 months) (p > 0.999). The median procedure time was similar in both groups (TRA, 81 minutes vs. TFA, 94 minutes; p = 0.570). No significant dose differences were found between the TRA and TFA groups in the dose-area product (median Gycm², 95 [range, 44-255] for TRA and 84 [34-255] for TFA; p = 0.678) or cumulative air kerma (median mGy, 609 [236-1584] for TRA and 634 [217-1594] for TFA; p = 0.551). No major adverse events occurred in either of the groups. Conclusion: PAE via TRA is a safe and feasible method comparable to conventional TFA. It can be safely implemented by selecting patients with patent carpal circulation and adequate height.

• 한국응급구조학회지
• /
• 제11권3호
• /
• pp.175-189
• /
• 2007

Background and Purpose : Higher grade students in elementary schools are most adequate subjects for first aid training. The purpose of this study was to assess first aid education and needs of higher grade students in elementary schools. Method : The subjects of this study were 183 higher grade students from 8 elementary schools. Data were collected by the questionnaire during the period from March 19 to April 13, 2007. The data were analyzed through frequency, Cronbach's ${\alpha}$, Independent Two samples t-test, One Way ANOVA by SPSS win 12.0. Result : 1. It showed that 78.1%(143 persons) of sujects answered that they learned first aid. 65% of sujects learned in the school(65%). 61.2% of sujects were taught by health teachers. 36.7%(67 person) of subjects was educated using practice with demonstration including lecture. Learned contents were action at emergency(50.8%), CPR(36.6%), splint (33.9%). 2. It showed that 90.2%(165 persons) of subjects answered that first aid and CPR education are necessary. Also 74.9%(137 persons) of subjects answered that will be educated first aid and CPR if opportunities is given. The 53.3%(73 persons) of subjects wanted teaching method using practice with demonstration including lecture. 3. The total mean showed $2.29{\pm}.48$ in needs of first aid education by 3 points Likert scale. Needs of first aid education was ranked Heimlich maneuver($2.41{\pm}.65$), splint and bandaging($2.38{\pm}.59$). Priority of intensive training showed patient assessment(38.0%) and CPR(19.7%) in first, splint and bandging(22.6%), CPR(21.9%) and Heimlich maneuver(21.9%) in second. 4. The needs assessment of first aid education showed statistically significant differences according to teaching method(F = 2.563, p = .025), education necessity yes or no(F = 2.474, p = .015), attending future education yes or no(F = 2.253, p = .026). Conclusion : These results suggest that First aid education for higher grade students in elementary schools must be consisted of most adequate content and method based on current education condition and needs assessment.

• Molecules and Cells
• /
• 제42권4호
• /
• pp.292-300
• /
• 2019

Immunometabolism, defined as the interaction of metabolic pathways with the immune system, influences the pathogenesis of metabolic diseases. Metformin and carbon monoxide (CO) are two pharmacological agents known to ameliorate metabolic disorders. There are notable similarities and differences in the reported effects of metformin and CO on immunometabolism. Metformin, an anti-diabetes drug, has positive effects on metabolism and can exert anti-inflammatory and anti-cancer effects via adenosine monophosphate-activated protein kinase (AMPK)-dependent and AMPK-independent mechanisms. CO, an endogenous product of heme oxygenase-1 (HO-1), can exert anti-inflammatory and antioxidant effects at low concentration. CO can confer cytoprotection in metabolic disorders and cancer via selective activation of the protein kinase R-like endoplasmic reticulum (ER) kinase (PERK) pathway. Both metformin and CO can induce mitochondrial stress to produce a mild elevation of mitochondrial ROS (mtROS) by distinct mechanisms. Metformin inhibits complex I of the mitochondrial electron transport chain (ETC), while CO inhibits ETC complex IV. Both metformin and CO can differentially induce several protein factors, including fibroblast growth factor 21 (FGF21) and sestrin2 (SESN2), which maintain metabolic homeostasis; nuclear factor erythroid 2-related factor 2 (Nrf2), a master regulator of the antioxidant response; and REDD1, which exhibits an anticancer effect. However, metformin and CO regulate these effects via different pathways. Metformin stimulates p53- and AMPK-dependent pathways whereas CO can selectively trigger the PERK-dependent signaling pathway. Although further studies are needed to identify the mechanistic differences between metformin and CO, pharmacological application of these agents may represent useful strategies to ameliorate metabolic diseases associated with altered immunometabolism.

• 한국환경과학회지
• /
• 제21권8호
• /
• pp.977-988
• /
• 2012

This study analyzed the characteristics of stormwater runoff by rainfall type in orchard areas and transportation areas for 2 years(2010~2011year). Effluents were monitored to calculate the Event Mean Concentrations(EMCs) and runoff loads of each pollutant. The pollutant EMCs by volume of stormwater runoff showed the ranges of BOD 0.9~13.6 mg/L, COD 13.7~45.2 mg/L, SS 4.1~236.4 mg/L, T-N 2.123~21.111 mg/L, T-P 0.495~2.214 mg/L in the orchard areas, and was calculated as BOD 2.3~22.5mg/L, COD 4.4~91.1 mg/L, SS 4.3~138.3 mg/L, T-N 0.700~13.500 mg/L, T-P 0.082~1.345 mg/L in the transportation areas. The correlation coefficient of determination in the orchard area was investigated in the order of Total Rainfall(0.81) > Total Runoff(0.76) > Rainfall Intensity(0.56) > Rainfall Duration(0.46) > Antecedent Dry Days(0.27). Also, in the case of the transportation area was investigated in the order of Total Rainfall (0.55) > Total Runoff(0.54) > Rainfall Intensity(0.53) > Rainfall Duration(0.24) > Antecedent Dry Days(0.14). As the result, comparing valuables relating to runoff of non-pollutant source between orchard areas and transportation areas, orchard area($R^2{\geq}0.5$ : X3, X4, X5) was investigated to have more influence of diverse independent valuables compared to the transportation area($R^2{\geq}0.5$ : X3, X4) and the difference of discharge influence factor by the land characteristics appeared apparently.