• 한국해양바이오학회지
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• 제1권4호
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• pp.243-251
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• 2006

Dideoxypetrosynol A, a polyacetylene from the marine sponge Petrosia sp., is known to exhibit significant selective cytotoxic activity against a small panel of human tumor cell lines, however, the mechanisms of which are poorly understood. In the present study, it was investigated the further possible mechanisms by which dideoxytetrosynol A exerts its anti-proliferative action in cultured human leukemia cell line U937. We observed that the proliferation-inhibitory effect of dideoxypetrosynol A was due to the induction of G1 arrest of the cell cycle and apoptosis, which effects were associated with up-regulation of cyclin D1 and down-regulation of cyclin E without any change in cyclin-dependent-kinases (Cdks) expression. Dideoxypetrosynol A markedly induced the levels of Cdk inhibitor p16/INK4a expression. Furthermore, down-regulation of phosphorylation of retinoblastoma protein (pRB) by this compound was associated with enhanced binding of pRB and the transcription factor E2F-1. The increase in apoptosis was associated with a dose-dependent up-regulation in pro-apoptotic Bax expression and activation of caspase-3 and caspase-9. Dideoxytetrosynol A decreased the levels of cyclooxygenase (COX)-2 mRNA and protein expression without significant changes in the levels of COX-1, which was correlated with a decrease in prostaglandin E2 (PGE2) synthesis. Furthermore, dideoxytetrosynol A treatment markedly inhibited the activity of telomerase, and the expression of human telomerase reverse transcriptase (hTERT), a main determinant of the telomerase enzymatic activity, was progressively down-regulated by dideoxytetrosynol A treatment in a dose-dependent fashion. Taken together, these findings provide important new insights into the possible molecular mechanisms of the anti-cancer activity of dideoxytetrosynol A.

• 대한한의학회지
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• 제26권1호
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• pp.26-36
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• 2005

Objective : Many traditional herbal remedies exhibit several beneficial effects including anti-inflammation. Euonymus alatus (Thunb.) Sieb (EA), known as Gui jun woo in Korea, has long been used in folk medicine to regulate Qi (bodily energy) and blood circulation, relieve pain, eliminate stagnant blood, and treat dysmenorrhea in oriental countries. The exact mechanism of the anti-inflammatory action of Euonymus alatus (Thunb.) Sieb (EA), however, has not been determined. Methods: Since there is increasing evidence that nitric oxide (NO) plays a crucial role in the pathogenesis of inflammatory diseases, this study was undertaken to address whether the methanol (MeOH) extract and its fractions of the bark of EA could modulate the expression of inducible NO synthase (iNOS) in thioglycollate-elicited murine peritoneal macrophages and murine macrophage cell line, RA W264.7 cells. Results: Stimulation of the peritoneal macrophages and RAW264.7 cells with $interferon-\gamma\;(IFN-\gamma)$ and lipopolysaccharide (LPS) resulted in increased production of NO in the medium. However, the butanol (BuOH) fraction of the MeOH extract of EA barks showed marked inhibition of NO synthesis in a dose-dependent manner. The inhibition of NO synthesis was reflected in the decreased amount of iNOS protein, as determined by Western blotting. The BuOH fraction did not affect the viability of RA W264.7 cells, as assessed by methylthiazol-2-yl-2, 5-diphenyl tetrazolium bromide (MTT) assay; rather, it reduced endogenous NO-induced apoptotic cell death via inhibition of NO synthesis in RAW264.7 cells. On the other hand, the MeOH and BuOH fraction showed no inhibitory effect on the synthesis of NO by RAW264.7 cells, when iNOS was already expressed by the stimulation with $IFN-\gamma$ and LPS. Conclusion: Collectively, these results demonstrate that the MeOH and BuOH fraction inhibits NO synthesis by inhibition of the induction of iNOS in murine macrophages.

• 한국동물생명공학회지
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• 제36권4호
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• pp.203-211
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• 2021

Diabetic mellitus (DM) is a carbohydrate metabolic disorder that involves high blood sugar because insulin works abnormally. Type 2 diabetes accounts for most of them. However, diabetes treatments such as GLP-1 and DPP-4 inhibitors commonly caused side effects including gastrointestinal disorders. Grifola frondosa (G. frondosa) revealed various pharmacological effects in recent studies. It has a variety of anti-cancer polysaccharides through host-mediated mechanisms. D-fraction in G. frondosa has apoptotic effects, promoting myeloid cell proliferation and differentiation into granulocytes-macrophages. It has also been shown to reduce the survival rate of breast cancer cells. Though, no further study has been conducted on the specific effects of G. frondosa in the db/db mouse. Therefore, we would like to research the blood glucose improving effect of G. frondosa, a natural material, in type 2 diabetes model mouse, in this study. G. frondosa was administered to the disease model mouse (BKS.Cg-+Lepr^db/+Lepr^db/OlaHsd) for 8 weeks to monitor weight and blood glucose changes every week. And we evaluated anti-diabetes effects by checking biomarker changes shown through blood. Experiment did not show statistically significant weight differences, but control groups showed significantly higher weight gain than G. frondosa administered groups. We collected blood from the tail veins of the db/db mouse each week. As a result, the lowest blood sugar level was shown in the 500 mg/kg group of G. frondosa. Glucose in the blood was examined with HBA1c, and 7.8% was shown in the 500 mg/kg administration group, lower than in other groups. These results suggest the potential improvements of diabetes in G. frondosa.

• 생명과학회지
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• 제34권2호
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• pp.138-144
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• 2024

Crocin은 여러 가지 요리에 향미와 색깔을 주는 치자 열매나 사프란에 함유되어 있는 적노란색의 수용성 색소이다. 사프란과 치자는 전통의학 분야에서 부종, 해열, 해독 작용이 있어 바이러스성 간염, 식도염, 관상동맥심장병, 신경쇠약, 불면증, 퇴행성 신경질환, 호흡기 질환, 비뇨기 질환 등을 치료하는데 사용되어 왔다. Crocin (C₄₄H₆₄O₂₄)은 카로테노이드의 복합체로, dicarboxylic acid crocetin과 disaccharide gentiobiose로 이루어진 diester이다. Crocin은 혈액학적인, 병리학적인 독성이나 유전독성이 없다. 현재까지 수많은 생체 내 및 생체 외 연구들을 통해 Crocin의 생물학적인 약리작용이 밝혀지고 있다. 본 총설에서는 염증성 장질환, 위염, 천식, 동맥경화, 류머티스 관절염, 다발성 경화증, 당뇨, 알츠하이머병, 파킨슨병, 우울증 등의 염증 관련 질환에서 Crocin의 보호 효과를 요약한다. Crocin은 다양한 작용 기전을 통해 항염, 항산화, 세포 자살 방지 기능을 함으로써 이들 질환을 개선하는 것으로 추론된다.

• 한방안이비인후피부과학회지
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• 제19권2호
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• pp.26-39
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• 2006

Objective : 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 performed 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 Progtaglandin E2 and Telomerase activity were measured Results : Exposure of A549 cells to CJGPT resulted in the growth inhibition and apoptosis in a dose-dependent manner as measured by MTT assay and fluorescent microscope. The antiuoliferative 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(WAF1/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 protaglandin E2 (PGE2) synthesis. CJGPT treatment also inhibited the levels of human telomerase reverse transcriptase (hTERT) and telomerase-associated protein (TEP)-1 mRNA expression, however the activity of telomerase was slightly increased by CJGPT treatment. 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.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제29권6호
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• pp.365-373
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• 2003

Tamoxifen is an selective estrogen receptor antagonist widely used in the management of patients with breast cancer for more than 30 years. It was thought to act primarily through occupying the estrogen receptor sites in ER positive breast cancer cells and directly on cancer cell proper. These inhibitory effects, which have been shown to be independent of the ER, highlight new mechanism of therapeutic action of tamoxifen. The purposes of this study were to identify ER in oral carcinoma cell lines and to evaluate ER independent cytotoxic effect of tamoxifen. KB(SCC), HSC-3(SCC) and A253(ACC) cell line were used and capacity of cell proliferation, apoptosis, in vitro invasion and gelatin zymography were tested. ER expression of each cell line were detected by RT-PCR and immunocytochemistry. Dose dependent inhibition of cell proliferation and inhibition of gelatinolytic activity were observed in all oral carcinoma cell lines and significant difference of apoptotic index were observed in A253 and KB. Tamoxifen inhibited in vitro invasion in all experimental groups. ER expression was detected in KB and A253. These data suggest that tamoxifen may play a role in management of oral carcinoma by independent cytotoxic effect and more advanced research must processed confirming ER-dependent cytotoxicity.

• 동의생리병리학회지
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• 제20권4호
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• pp.966-972
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• 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.

• Journal of Nutrition and Health
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• 제51권6호
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• pp.498-506
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• 2018

본 연구는 베타세포에서 라이코펜의 항사멸 효과와 그 기전에 대해 조사하기 위해 실시하였다. 라이코펜에 의한 베타세포독성을 조사하기 위해 다양한 농도 (0.1, 1, 10 nM)로 처리하였을 경우, 저농도에서 세포독성이 나타나지 않음을 관찰하였다. 선택한 농도를 사이토카인 혼합물과 함께 처리하였을 경우, 세포 생존율이 증가하는 것을 관찰하였고, 세포사멸 유도 단백질인 Bax의 발현양은 감소하고, 세포사멸억제 단백질인 Bcl-2 발현양은 증가하는 것을 관찰하였다. 또한 사이토카인 혼합물에서 증가하였던 세포내 산화스트레스가 라이코펜과 함께 처리하였을 경우 감소되는 것을 관찰하였고 이러한 효과는 항산화 유전자인 GCLC, NQO1, HO-1의 발현양이 증가함으로서 일어난 현상임을 알 수 있었다. 라이코펜은 미토콘드리아의 생성 및 기능과 관련된 유전자의 발현을 증가시키고 사이토카인 혼합물에 의해 감소되었던 세포내 ATP 생성량을 증가시켰다. 이러한 결과는 라이코펜의 항산화효과와 미토콘드리아 기능 개선 효과가 사이토카인에 의한 베타세포 사멸을 억제하는 기전 중의 하나로 작용할 수 있음을 의미한다. 향후 라이코펜이 베타세포를 타겟으로 하는 제 2형 당뇨 치료의 기능성 소재로 개발될 가능성이 있음을 시사하는 바이다.

• 동의생리병리학회지
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• 제20권1호
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• pp.163-170
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• 2006

Nardostachyos Rhizoma (N. Rhizoma) belonging to the family Valerianaceae has been anti-arrhythmic effect, and sedation to the central nerve and a smooth muscle. We reported that the water extract of N. Rhizoma induced apoptotic cell death and differentiation in human promyelocytic leukemia (HL-60) cells. Cytotoxicity of N. Rhizoma was detected only in HL-60 cells (IC50 is about 200 ${\mu}g/ml$). The cytotoxic activity of N. Rhizoma in HL-60 cells was increased in a dose-dependent manner. We used several measures of apoptosis to determine whether these processes were involved in N. Rhizoma-induced apoptotic cell death. The high-dose (200 ${\mu}g/ml$) treatment of N. Rhizoma to HL-60 cells showed cell shrinkage, cell membrane blobbing, apoptotic bodies, and the fragmentation of DNA, suggesting that these cells underwent apoptosis. Treatment of HL-60 cells with N. Rhizoma time-dependently induced activation of caspase-3, caspase-8, and caspase-9 and proteolytic cleavage of poly(ADP-ribose) polymerase. Also, we investigated the effect of N. Rhizoma on cellular differentiation and proliferation in HL-60 cells. Differentiation and proliferation of HL-60 cells was determined through expression of CD11b and CD14 surface antigens using flow cytometry and nitroblue tetrazolium (NBT) assay, and through analysis of cell cycle using propidium iodide assay, respectively. N. Rhizoma induced the differentiation of HL-60 at the low-dose (100 ${\mu}g/ml$) treatment, as shown by increased expression of differentiation surface antigen CD11b, but not CDl4 and increased reducing activity of NBT. When HL-60 cells were treated with N. Rhizoma at concentration of $50{\mu}g/ml\;and\;100{\mu}g/ml$, NBT-reducing activities induced approximately 1.5-fold and 20.0-fold as compared with the control. In contrast, HL-60 cells treated with the N. Rhizoma-ATRA combination showed markedly elevated levels of 26.3-fold at $50{\mu}g/ml$ N. Rhizoma-0.1 ${\mu}M$ ATRA combination and 27.5-fold at 50 ${\mu}g/ml$ N. Rhizoma-0.2 ${\mu}M$ ATRA combination than when treated with N. Rhizoma alone or ATRA alone. It may be that N. Rhizoma plays important roles in synergy with ATRA during differentiation of HL-60 cells. DNA flow-cytometry indicated that N. Rhizoma markedly induced a G1 phase arrest of HL-60 cells. N. Rhizoma-treated HL-60 cells increased the cell population in G1 phase from 32.71% to 42.26%, whereas cell population in G2/M and S phases decreased from 23.61% to 10.33% and from 37.78% to 33.98%, respectively. We examined the change in the $p21^{WAF1/Cip1}\;and\;p27^{Kip1}$ proteins, which are the CKIs related with the G1 phase arrest. The expression of the CDK inhibitor $p27^{Kip1},\;but\;not\;p21^{WAF1/Cip1}$ were markedly increased by N. Rhizoma. Taken together, these results demonstrated that N. Rhizoma induces apoptotic cell death through activation of caspase-3, and potently inhibits the proliferation of HL-60 cells via the G1 phase cell cycle arrest in association with $p27^{Kip1}$ and granulocytic differentiation induction .

• Tuberculosis and Respiratory Diseases
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• 제54권4호
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• pp.403-414
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• 2003

연구배경 : Proteasome 억제가 세포의 apoptosis에 미치는 영향은 세포 종류에 따라 차이를 보이고 있다. 그러나 아직까지 폐암 세포에서 proteasome 억제가 미치는 효과 및 그 기전에 관해서는 확실하게 규명되어 있지 못한 상태이다. 본 연구에서는 폐암 세포주에서 proteasome 억제에 의한 apoptosis의 유도 유무를 관찰하고, 그 기전을 규명하고자 하였다. 방 법 : 폐암 세포주인 A549와 NCI-H157 세포에 proteasome 억제제인 MG132와 PS-341을 투여하고 세포의 생존율을 MTT 분석으로 평가하였고, apoptosis 유무를 PARP 단백에 대한 Western 분석으로 확인하였다. Proteasome 억제가 caspase 3와 JNK의 활성화에 미치는 효과를 각각 Western 분석과 immunocomplex kinase 분석으로 평가하였다. Proteasome 억제제를 투여하고 항 apoptosis 경로인 ERK와 cIAP1에 미치는 효과를 Western 분석으로 평가하였다. 결 과 : A549와 NCI-H157 세포에 MG132를 투여하였을 때, 세포생존율의 감소가 관찰되었고, 이는 apoptosis의 유도에 의한 것으로 확인되었다. MG132와 PS-341 처치로 caspase 3와 JNK가 활성화되었다. 반면에 활성화된 ERK의 발현과 cIAP1의 발현은 감소하였다. 결 론 : 폐암 세포에서 proteasome 억제에 의한 apoptosis에는 caspase 3, JNK와 같은 apoptosis 유도 경로의 활성화와 함께 항 apoptosis 경로의 억제가 관여할 것으로 생각된다.