• 제목/요약/키워드: inhibitory mechanism

검색결과 1,033건 처리시간 0.029초

Induction of Cyclin D1 Proteasomal Degradation by Branch Extracts from Abeliophyllum distichum Nakai in Human Colorectal Cancer Cells

  • Park, Gwang Hun;Park, Jae Ho;Jeong, Jin Boo
    • 한국자원식물학회지
    • /
    • 제28권6호
    • /
    • pp.682-689
    • /
    • 2015
  • Abeliophyllum distichum Nakai (A. distichum) has been reported to exert the inhibitory effect on angiotensin converting enzyme and aldose reductase. Recently, our group found that branch extracts of A. distichum (EAFAD-B) induce apoptosis through ATF3 activation in human colon cancer cells. However, anti-cancer reagents exert their activity through the regulation of various molecular targets. Therefore, the elucidation of potential mechanisms of EAFAD-B for anti-cancer activity may be necessary. To elucidate the potential mechanism of EAFAD-B for anti-cancer activity, we evaluated the regulation of cyclin D1 in human colon cancer cells. EAFAD-B decreased cellular accumulation of cyclin D1 protein. However, cyclin D1 mRNA was not changed by EAFAD-B. Inhibition of proteasomal degradation by MG132 attenuated EAFAD-B-mediated cyclin D1 downregulation and the half-life of cyclin D1 was decreased in the cells treated with EAFAD-B. In addition, EAFAD-B induced cyclin D1 phosphorylation at threonine-286 and the point mutation of threonine-286 to alanine attenuated EAFAD-B-mediated cyclin D1 proteasomal degradation. Inhibitions of both ERK1/2 by PD98059 and NF-κB by a selective inhibitor, BAY 11-7082 suppressed cyclin D1 downregulation by EAFAD-B. From these results, we suggest that EAFAD-B-mediated cyclin D1 downregulation may result from proteasomal degradation through its threonine-286 phosphorylation via ERK1/2-dependent NF-κB activation. The current study provides new mechanistic link between EAFAD-B and anti-cancer activity in human colon cancer cells.

Water Extracts of Anthriscus sylvestris Leaf induces Apoptosis in FaDu Human Hypopharynx Squamous Carcinoma Cells

  • Yang, Jung Eun;Lee, Seul Ah;Moon, Sung Min;Han, Seul Hee;Choi, Yun Hee;Kim, Su-Gwan;Kim, Do Kyung;Park, Bo-Ram;Kim, Chun Sung
    • International Journal of Oral Biology
    • /
    • 제42권2호
    • /
    • pp.47-54
    • /
    • 2017
  • Anthriscus sylvestris (L.) Hoffm. is a perennial herb found widely distributed in various regions of Korea, Europe, and New Zealand. The root of A. sylvestris have been extensively used in the treatment for antitussive, antipyretic, cough remedy in Oriental medicine, but the physiologically active function of the leaf of A. sylvestris is as yet unknown. In this study, we investigated the anti-cancer activity and the mechanism of cell death of water extracts of leaf of Anthriscus sylvestris (WELAS), on human FaDu hypopharyngeal squamous carcinoma cells. Our data showed that WELAS treatment inhibited cell viability in a concentration- and time-dependent manner. In addition, the treatment of WELAS markedly induced apoptosis in FaDu cells, as determined by the viability assay, DAPI stain and FACS analysis. WELAS also increased the proteolytic cleavage of procaspase-3, -9 and PARP (poly(ADP-ribose) polymerase). In addition, exposure to WELAS decreased the expression of Bcl-2 (an anti-apoptotic factor), but increased the expression of Bax (a pro-apoptotic factor), suggesting that mitochondria-dependent apoptotic pathways are mediated in WELAS-induced apoptosis. Taken together, these results indicate that water extracts of leaf of A. sylvestris inhibits cell growth and induces apoptosis via the mitochondrial-dependent apoptotic pathway in FaDu human hypopharyngeal squamous carcinoma cells. Therefore, we propose that the water extracts of leaf of A. sylvestris is a novel chemotherapeutic drug, having growth inhibitory properties and induction of apoptosis in human oral cancer cells.

선방활명음(仙方活命飮)메탄올 추출물이 LPS로 유도된 Raw 264.7 Cell에서의 Pro-inflammatory Mediator에 미치는 영향 (Inhibitory Effect of Sunbanghwalmyungeum MeOH Extract on Pro-inflammatory Mediator in Lipopolysaccharide - activated Raw 264.7 Cells)

  • 최송이;조미정;김상찬;변성희
    • 대한본초학회지
    • /
    • 제23권3호
    • /
    • pp.11-18
    • /
    • 2008
  • SunBangHwalMyungEum (SBH) has the effects of subduing swelling, resolving masses and alleviating pain in traditional oriental medicine. Recent studies showed that SunBangHwalMyungEum produced anti-cancer, anti-metastasis and immuno-modulatory effects. However there is lack of studies regarding the effects of SBH on the immunological activities. The present study was conducted to evaluate the effect of SBH on the regulatory mechanism of cytokines and nitric oxide (NO) in Raw 264.7 cells. Methods : After the treatment of SBH, cell viability was measured by MTT assay, NO production was monitored by measuring the nitrite content in culture medium. Inducible nitric oxide synthase (iNOS) was determined by immunoblot analysis, and levels of cytokine were analyzed by sandwich immunoassays. Results : Results provided evidence that SBH inhibited the production of NO, iNOS, $interleukin-1{\beta}$ ($(IL-1{\beta})$), IL-6, and the activation of phospholylation of inhibitor ${\kappa}B{\alpha}$ in Raw 264.7 cells activated with lipopolysaccharide. Conclusions : These findings suggest that SBH can produce anti-inflammatory effect, which may play a role in adjunctive therapy in Gram-negative bacterial infections.

  • PDF

Acetonitrile 용액중에서 살충제 O, O-Dimethyl-O-(3-Methyl-4-Nitrophenyl)-Phosphorothioate (Fenitrothion)의 전기화학적 환원 (On the Electrochemical Reduction of O, O-Dimethyl-O-(3-Methyl-4-Nitrophenyl)-Phosphorthioate (Fenitrothion) Pesticide in Acetonitrile Solution)

  • 김일광;김윤근;천현자
    • 대한화학회지
    • /
    • 제32권3호
    • /
    • pp.186-194
    • /
    • 1988
  • 계면활성 micelle을 형성하는 acetonitrile 용액을 O,O-dimethyl-O-(3-methyl-4-nitrophenyl)-phosphorothioate (Fenitrothion)의 전기화학적 환원을 direct current 및 differential pulase polarography, cyclic voltammetry 그리고 controlled potential coulometry 방법으로 연구하였다. Fenitrothion의 환원과정은 1단계로 4 전자 이동에 의한 부분 가역적 전자이동 화학반응(EC, EC)기구로 O,O-dimethyl-O-(3-methyl-4-hydroxyaminophenyl)-phosphorothioate를 형성하고, 더 높은 음전위에서 2 전자 이동에 따른 양성자 반응으로 phosphorus 원자와 phenoxy group의 단일 결합이 끊어지면서 주 생성물인 p-amino-m-cresol과 dimethyl thiophosphinic acid를 생성하였다. Sodium lauryl sulfate micelle 용액에서 polarography 환원파는 전체적으로 억제 되었으며 특히 1차 환원파는 음이온 micelle의 선택적 작용으로 2단계로 분리되었다.

  • PDF

鷄胚筋原細胞의 融合에 미치는 카테콜아민의 影響 (Effects of Catecholamine on the Fusion of Chick Embryo Myoblasts in vitro)

  • Kang, Man-Sik;Ha, Doo-Bong;Lee, Chung-Choo;Park, Yung-Chul;Hyockman Kwon
    • 한국동물학회지
    • /
    • 제27권2호
    • /
    • pp.73-84
    • /
    • 1984
  • 근원세포가 분화하는 과정에서 신경전달물질의 영향을 연구하기 위하여 배양한 근세포에 dopamine과 epinephrine을 처리하여 근원세포의 융합과 세포내 cAMP의 농도에 미치는 효과를 조사하였다. Dopamine $(3\\times10^{-5}M)$과 epinephrine $(3\\times10^{-5}M)$을 세포배양후 34시간에 처리했을 때 근원세포의 융합이 크게 억제되었으며, 특히 dopamine의 효과가 epinephrine보다 현저하게 나타났다. 한편, 세포내 cAMP농도는 dopamine과 epinephrine을 처리해도 거의 변화가 없었다. 근원세포의 분화에 cAMP가 관계하는지를 조사하기 위해 dbcAMP, $PGE_1$ 및 aspirin을 처리하였는데, dbcAMP $(1\\times10^{-4}M)$는 근원세포의 융합을 억제한 반면, $PGE_1 (3\\times10^{-6}M)$은 오히려 융합을 촉진하였고, PG 합성효소의 억제물질인 aspirin은 융합 억제효과를 보였다. Dopamine과 epinephrine이 근원세포의 융합과정에 작용하는 가능성있는 기작에 대해서 고찰하였다.

  • PDF

Benzo(a)pyrene의 돌연변이원성에 대한 유기게르마늄(GE-132)의 항돌연변이 효과 (Antimutagenic Effect of Organic Germanium(GE-132) on the Mutagenicity of Benzo(a)pyrene)

  • 이효민;정용;정기화;김재완;권순경
    • 약학회지
    • /
    • 제37권1호
    • /
    • pp.18-29
    • /
    • 1993
  • This study was initiated to investigate the effective action and mechanism of GE-132 (Carboxyethylgermanium sesquioxide)on benzo(a)pyrene, which have strong carcinogenicity and mutagenicity. To confirm desmutagenic effect (inhibition of metabolic processes of benzo(a)pyrene with S9 Mix or inactivation of the mutagenicity of benzo(a)pyrene metabolites) and antimutagenic effect (inhibition of gene-expression of reverted genes) of GE-132 against benzo(a)pyrene using with Salmonella typhimuyium TA98 Ames test was performed. The revertants in desmutagenicity test were decreased significantly in the combined groups of benzo(a)pyrene and GE-132 than benzo(a)pyrene only, without inhibition the metabolism of benzo(a)pyrene by S9 Mix. The ideal combined groups of benzo(a)pyrene and GE-132 were 10 $\mu{M}$ and 10mg, 20 $\mu{M}$ and 20mg, 100 $\mu{M}$ and 30 mg, respectively. Then, the revertants in antimutagenicity test, which was studied the direct action of GE-132 on the induction of revertant cells by Salmonella typhimurium TA98 and activated benzo(a)pyrene were decreased significantly in the treated groups of GE-132 than no treated groups. The number of revertants of Salmonella typhimurium TA98 were reduced with increasing amounts of GE-132. From the above results, it was found that GE-132 inactivated the mutagenic metabolites of benzo(a)pyrene without inhibition of the enzyme action in the S9 Mix, and GE132 showed antimutagenic effect which have inhibitory action of reverted gene expression.

  • PDF

홍화자, 향부자, 형개 추출물의 미백효과에 관한 연구 (A Study on the Depigmenting Effect of Carthamus tinctorius Seed, Cyperus rotundus and Schizonepeta tenuifolia Extracts)

  • 황은영;김동희;황주영;김희정;박태순;이인선;손준호
    • 한국식품과학회지
    • /
    • 제44권1호
    • /
    • pp.76-81
    • /
    • 2012
  • 본 연구에서는 3가지 홍화자, 향부자, 형개 추출물의 미백효과를 연구하였다. 멜라닌 생성 첫 단계인 tyrosinase 억제활성과 멜라닌 생성 억제효과를 측정한 결과, 홍화자 에탄올 추출물이 tyrosinase 활성과 B16F10 melanoma 세포의 멜라닌 생성 억제하였다. 그 결과, 홍화자 추출물은 B16F10 melanoma 세포에서 melanogenesis 따른 tyrosinase 형성 억제에 따른 멜라닌 합성 관련 인자 MITF, tyrosinase, TRP-1, TRP-2 의 발현을 억제함에 따라 홍화자 추출물의 미백효과를 확인하였다. 따라서 홍화자는 미백효과를 가진 천연 기능성 재료로서 가능성이 매우 높은 것으로 판단된다.

마황천오 약침액이 3T3-L1 지방세포 분화 및 유전자발현에 미치는 영향 (Effects of Mahuang-Chuanwu(Mahwang-Cheonoh) Pharmacopuncture Solution on Adipocyte Differentiation and Gene Expression in 3T3-L1 Adipocytes)

  • 강경화
    • Korean Journal of Acupuncture
    • /
    • 제31권4호
    • /
    • pp.168-178
    • /
    • 2014
  • Objectives : Mahuang-Chuanwu(Mahwang-Cheonoh) Pharmacopuncture(MCP) has been used to treat obesity in Clinical Korean Medicine. MCP solution(MCPS) is also expected to have strong anti-obesity activities. However, little is known about the mechanisms of its inhibitory effects on adipocyte differentiation and lipogenesis. Methods : In the present study, we examined the effects of MCPS on differentiation and lipogenesis of 3T3-L1 adipocytes. To elucidate the mechanism of the effects of MCPS on lowering lipid content in 3T3-L1 adipocytes, we examined whether MCPS modulates the expressions of transcription factors to induce lipogenesis and adipogenic genes related to regulate the accumulation of lipids. Results : Our results showed that MCPS significantly inhibited differentiation and lipogenesis of 3T3-L1 adipocytes in a dose-dependent manner. MCPS suppressed the mRNA expressions of cytidine-cytidine-adenosine-adenosine-thymidine(CCAAT)/enhancer binding proteins ${\alpha}$($C/EBP{\alpha}$), C/EBP ${\beta}$, $C/EBP{\delta}$, and peroxisome proliferator-activated receptor ${\gamma}$($PPAR{\gamma}$) genes related to the induction of adipose differentiation. MCPS inhibited the mRNA expressions of adipose-specific aP2, adipsin, lipoprotein lipase(LPL), CD36, TGF-${\beta}$, and leptin genes related to the fat formation. MCPS downregulated the mRNA expressions of liver X receptor(LXR) ${\alpha}$ and fatty acid synthase(FAS) genes related to the induction of lipogenesis. In addition, MCPS reduced the production of adipocyte-induced pro-inflammatory cytokines. Conclusions : MCPS could regulate the accumulation of lipids and expression of adipogenic genes via inhibition of transcript factors related to induction of adipose differentiation.

Oxymatrine Causes Hepatotoxicity by Promoting the Phosphorylation of JNK and Induction of Endoplasmic Reticulum Stress Mediated by ROS in LO2 Cells

  • Gu, Li-li;Shen, Zhe-lun;Li, Yang-Lei;Bao, Yi-Qi;Lu, Hong
    • Molecules and Cells
    • /
    • 제41권5호
    • /
    • pp.401-412
    • /
    • 2018
  • Oxymatrine (OMT) often used in treatment for chronic hepatitis B virus infection in clinic. However, OMT-induced liver injury has been reported. In this study, we aim to investigate the possible mechanism of OMT-induced hepatotoxicity in human normal liver cells (L02). Exposed cells to OMT, the cell viability was decreased and apoptosis rate increased, the intracellular markers of oxidative stress were changed. Simultaneously, OMT altered apoptotic related proteins levels, including Bcl-2, Bax and pro-caspase-8/-9/-3. In addition, OMT enhanced the protein levels of endoplasmic reticulum (ER) stress makers (GRP78/Bip, CHOP, and cleaved-Caspase-4) and phosphorylation of c-Jun N-terminal kinase (p-JNK), as well as the mRNA levels of GRP78/Bip, CHOP, caspase-4, and ER stress sensors (IREI, ATF6, and PERK). Pre-treatment with Z-VAD-fmk, JNK inhibitor SP600125 and N-acetyl-l-cysteine (NAC), a ROS scavenger, partly improved the survival rates and restored OMT-induced cellular damage, and reduced caspase-3 cleavage. SP600125 or NAC reduced OMT-induced p-JNK and NAC significantly lowered caspase-4. Furthermore, 4-PBA, the ER stress inhibitor, weakened inhibitory effect of OMT on cells, on the contrary, TM worsen. 4-PBA also reduced the levels of p-JNK and cleaved-caspase-3 proteins. Therefore, OMT-induced injury in L02 cells was related to ROS mediated p-JNK and ER stress induction. Antioxidant, by inhibition of p-JNK or ER stress, may be a feasible method to alleviate OMT-induced liver injury.

STAT3 활성 억제를 유도하는 resveratrol의 호르몬 불응성 전립선 암 예방 효과 (Resveratrol Prevents Hormone-refractory Prostate Cancer Cell Growth via Inhibition of STAT3 Activity)

  • 조석철;최부영
    • 한국식품과학회지
    • /
    • 제46권4호
    • /
    • pp.516-521
    • /
    • 2014
  • 전립선암은 발병률이 높은 암종 중에 하나이다. 전립선 치료제인 flutamide는 androgen 수용체의 호르몬 치료제로서 내성효과에 대한 기본 메커니즘은 명확하지 않다. 본 연구에서는 flutamide에 의해 유도되는 호르몬 불응성 전립선 암세포 성장에서 포도 성분인 resveratrol의 억제효과를 조사하였다. 본 연구의 결과를 통해 호르몬 비의존적인 신호전달의 전환으로 유발되는 호르몬 불응성 전립선 암에서 resveratrol은 예방 및 항암효과에 기여할 것이라 판단된다.