• 제목/요약/키워드: cancer cell growth inhibition

검색결과 819건 처리시간 0.026초

Anticancer Activity of Acanthopanax trifoliatus (L) Merr Extracts is Associated with Inhibition of NF-κB Activity and Decreased Erk1/2 and Akt Phosphorylation

  • Wang, Hua-Qian;Li, Dong-Li;Lu, Yu-Jing;Cui, Xiao-Xing;Zhou, Xiao-Fen;Lin, Wei-Ping;Conney, Allan H.;Zhang, Kun;Du, Zhi-Yun;Zheng, Xi
    • Asian Pacific Journal of Cancer Prevention
    • /
    • 제15권21호
    • /
    • pp.9341-9346
    • /
    • 2014
  • Acanthopanax trifoliatus (L) Merr (AT) is commonly used as an herbal medicine and edible plant in some areas of China and other Asian countries. AT is thought to have anticancer effects, but potential mechanisms remain unknown. To assess the anticancer properties of AT, we exposed prostate cancer cells to AT extracts and assessed cell proliferation and signaling pathways. An ethanol extract of AT was suspended in water followed by sequential extraction with petroleum ether, ethyl acetate and n-butanol. PC-3 cells were treated with different concentrations of each extract and cell viability was determined by the MTT and trypan blue exclusion assays. The ethyl acetate extract of the ethanol extract had a stronger inhibitory effect on growth and a stronger stimulatory effect on apoptosis than any of the other extracts. Mechanistic studies demonstrated that the ethyl acetate extract suppressed the transcriptional activity of NF-${\kappa}B$, increased the level of caspase-3, and decreased the levels of phospho-Erk1/2 and phospho-Akt. This is the first report on the anticancer activity of AT in cultured human prostate cancer cells. The results suggest that AT can provide a plant-based medicine for the treatment or prevention of prostate cancer.

Schizandrin의 신혈관형성억제에 의한 항암효과 (Antitumor Effect of Schizandrin by Inhibiting Angiogenesis)

  • 윤미소;김도윤;유호진;박주훈;장상희;원경종;김보경;이환명
    • 동의생리병리학회지
    • /
    • 제26권5호
    • /
    • pp.687-692
    • /
    • 2012
  • Schizandra chinensis extract has been known to possess a variety of efficacy including antitumor. However, it remains unclear how schizandrin, which is a major biological active ingredient of Schizandra chinensis, exerts antitumor effect. This study was designed to investigate the mechanism by which schizandrin inhibits tumor growth and metastasis. In in vivo test using tumor model mice injected with B16BL6 cell line, mice treated with 10 and 100 ${\mu}g/ml$ schizandrin showed a significant inhibition by $73.79{\pm}6.43%$ and $90.46{\pm}1.72%$, respectively, compared with positive tumor controls. Schizandrin did not exert a significant toxicity for the normal cells (HUVECs) and tumor cell lines (A549, B16BL6, Du145, Huh7). Treatment with schizandrin at 10 and 100 ${\mu}g$/head significantly inhibited the tumor-induced angiogenesis by $68.04{\pm}32.21%$ and $103.8{\pm}34.99%$ compared with the positive control group, respectively. Using in vivo lung metastasis model, tumor metastasis assay revealed that 10 and 100 ${\mu}g$/head schizandrin significantly decreased the metastatic lung tumor by $37.51{\pm}8.15%$ and $75.53{\pm}4.38%$ compared with positive controls, respectively. On the other hand, schizandrin did not affect the adherence of B16BL6 cell line to extracellular matrix protein. These results demonstrate that schizandrin exerts inhibitory effect on tumor growth and metastasis by inhibiting angiogenesis. This study thus suggest that schizandrin may be a candidate molecule target for cancer drug development.

사람혀편평상피세포암종세포에서 proteasome 억제제인 lactacystin에 의해 유도된 세포자멸사의 기전에 대한 연구 (Mechanism Underlying a Proteasome Inhibitor, Lactacystin-Induced Apoptosis on SCC25 Human Tongue Squamous Cell Carcinoma Cells)

  • 백철중;김규천;김인령;이승은;곽현호;박봉수;태일호;고명연;안용우
    • Journal of Oral Medicine and Pain
    • /
    • 제34권3호
    • /
    • pp.261-276
    • /
    • 2009
  • Sreptomyces라는 세균에서 추출한 lactacystin은 선택적인 proteasome 억제제로서 많은 연구에서 사용되어져 왔다. Proteasome 억제제는 최근의 많은 연구를 통해서 암세포증식의 억제에 대한 효과가 증명되었으며, 특히 다른 항암제와 병용처리 시, 상호작용에 의한 상승효과가 있다고 알려져 있다. 현재 proteasome 억제제는 새로운 강력한 항암제로서 분류되어 있다. 본 연구는 사람혀편평세포암종세포(SCC25 cells)에서 lactacystin의 세포독성과 성장억제 효과, 그리고 세포자멸사의 유도에 대한 분자생물학적 기전을 밝히기 위해 실험을 시행하였다. SCC25 세포, 사람정상각화세포 (HaCaT cells) 그리고 사람치은섬유모세포(HGF-1 cells)의 생존율 측정은 MTT법을 시행하였고, SCC25 세포의 성장억제를 확인하기 위해서는 clonogenic assay를 사용하였다. lactcystin이 SCC25 세포에서 세포자멸사가 유도되는지를 확인하기 위해서 hoechst 염색법, hemacolor 염색법 그리고 TUNEL법을 시행하였다. 그리고 SCC25 세포에 lactacystin을 적용한 후, Western blot 분석, 세포면역화학염색, 공초점레이저주사현미경 검경, FACScan flow cytometry, 사립체막 전위변화, proteasome 활성도 측정 등을 시행하였다. Lactacystin으로 처리된 SCC25 세포는 시간 및 용량 의존적인 세포생존율의 감소, 용량의존적인 세포성장억제 그리고 세포자멸사에 의한 세포죽음을 보였다. 흥미롭게도 lactacytin은 정상세포인 HaCat 세포와 HGF-1 세포에서는 세포독성을 전혀 보이지 않았다. 그리고 lactacystin이 적용된 SCC25세포에서 핵 응축, DNA의 조각남, 사립체막전위와 proteasome 활성도의 감소, DNA 양의 감소, cytochrome c의 사립체에서의 세포질로의 유리, AIF와 DFF40 (CAD)의 핵으로의 이동, Bax의 증가, caspase-7, caspase-3, PARP, lamin A/C 그리고 DFF45 (ICAD)의 활성화 혹은 파괴와 같은 아주 다양한 세포자멸사 증거를 보였다. Flow cytometry 분석에서는 CDK 억제제인 $p21^{WAF1/CIP1}$$p27^{KIP1}$의 발현 증가와 관계있는 것으로 추정되어 지는 G1 세포주기 정지를 보였다. 이러한 결과는 lactacytin이 SCC25 세포에서 G1 세포주기정지와 proteasome, 사립체 및 caspase 경로의 연속반응을 통한 세포자멸사를 유도함을 명확하게 증명하고 있다. 이와 같은 세포주기 정지와 세포자멸사 유도능은 lactacytin이 사람혀편평상피세포암종의 새로운 치료전략으로서의 가능성을 제공한다고 생각한다.

활락효영단합인삼양위탕(活絡效靈丹合人蔘養胃湯)이 혈관신생(血管新生) 억제(抑制)에 미치는 영향(影響) (Effect of Whalakyuoleyng-dan plus Yinsamyangwui-tang on Anti-angionesis)

  • 고기완;박준혁;강희;김성훈;유영법;심범상;최승훈;안규석
    • 대한한방종양학회지
    • /
    • 제7권1호
    • /
    • pp.77-97
    • /
    • 2001
  • Anti-angiogenesis is one of therapies which have been high-lightened on the research of cancer treatment. Anti-angiogenesis means that new blood vessels are created from a existing capillary tube and it is a important process on metastasis and permeation when cancer is created or formed. Since angiogenesis have been under research, a complete recovery oriented treatment against cancer have been suggested blocking metastasis, delaying the growth of cancer cell, and blocking the supply of oxygen and nutritive substance through the web of blood vessels. Until now, there are several anti-angiogenesis, which have been known to the public, such as thalidomide, angiostatin, endostatin, 2-methoxyestradiol, TNP-470, and marimastat, etc. Additionally, 17 clinical testing projects about anti-angiogenesis are on the process in NCI(National Cancer Institute). Especially, TNP-470 showed effectiveness against cancer on clinical testing after finishing animal testing. Based on existing researches showing that Yinsamyangwui-tang is effective to strengthening body resistance and Whallakhyolenyng-dan effects cells on the inside of blood vessel because Whallakhyolenyng- dan restrains cell adhesion during the restraining period of a blood vessel, I tried to research the effect of Whalakhyolenyng-dan plus Yinsamyangwui-tang on angiogenesis. I made a conclusion putting into operation through using SK-Hep-1 (KCLB 30052), A549(KCLB 10185), AGS(KCLB 21739), and BCE(Bovine Capillary Endothelial Cell). Followings are the results of my experimental research: 1. According to the researching results of anti-cancer activation against cancer cell, Whallkhyoleyng dan plus Yinsamyangwui-tang decreased the number of cancer cells -- While injecting $600{\mu}g/ml$, injected groups decreased 3.1% more comparing with the contrastive group of SK-Hep-1, 49.7% more comparing with the contrastive group of A549, and 31.0% more comparing with the contrastive group of AGS. 2. According to the researching results of DNA composition effect between BCE and cancer cell, Whallakhyoleyng-dan plus Yinsamyangwui-tang reduced the rate of SK-Hep-1 synthesis inhibition by 59.1% at $600{\mu}g/ml$ intensity comparing with contrastive group; for A549, 72.6%; for AGS, 6.1%, for BCE, 28.9%. 3. According to the researching results about the effect of BCE cell to angiogenesis, angiogenesis was restrained at $400{\mu}g/ml$ intensity during 18 hours observation. 4. In the case of aortic ring assay, the half level of angiogenesis was reduced comparing with the contrastive group while injecting with $400{\mu}g/ml$ intensity; with $800{\mu}g/ml$, under 10% comparing with contrastive group; and with $1600{\mu}g/ml$, complete restrain. According to the above results, Whallakhyoleyng-dan plus Yinsamyangwui-tang was proved to have an anti-angiogenetic effects.

  • PDF

Systemic Approaches Identify a Garlic-Derived Chemical, Z-ajoene, as a Glioblastoma Multiforme Cancer Stem Cell-Specific Targeting Agent

  • Jung, Yuchae;Park, Heejoo;Zhao, Hui-Yuan;Jeon, Raok;Ryu, Jae-Ha;Kim, Woo-Young
    • Molecules and Cells
    • /
    • 제37권7호
    • /
    • pp.547-553
    • /
    • 2014
  • Glioblastoma multiforme (GBM) is one of the most common brain malignancies and has a very poor prognosis. Recent evidence suggests that the presence of cancer stem cells (CSC) in GBM and the rare CSC subpopulation that is resistant to chemotherapy may be responsible for the treatment failure and unfavorable prognosis of GBM. A garlic-derived compound, Z-ajoene, has shown a range of biological activities, including anti-proliferative effects on several cancers. Here, we demonstrated for the first time that Z-ajoene specifically inhibits the growth of the GBM CSC population. CSC sphere-forming inhibition was achieved at a concentration that did not exhibit a cytotoxic effect in regular cell culture conditions. The specificity of this inhibitory effect on the CSC population was confirmed by detecting CSC cell surface marker CD133 expression and biochemical marker ALDH activity. In addition, stem cell-related mRNA profiling and real-time PCR revealed the differential expression of CSC-specific genes, including Notch, Wnt, and Hedgehog, upon treatment with Z-ajoene. A proteomic approach, i.e., reverse-phase protein array (RPPA) and Western blot analysis, showed decreased SMAD4, p-AKT, 14.3.3 and FOXO3A expression. The protein interaction map (http://string-db.org/) of the identified molecules suggested that the AKT, ERK/p38 and $TGF{\beta}$ signaling pathways are key mediators of Z-ajoene's action, which affects the transcriptional network that includes FOXO3A. These biological and bioinformatic analyses collectively demonstrate that Z-ajoene is a potential candidate for the treatment of GBM by specifically targeting GBM CSCs. We also show how this systemic approach strengthens the identification of new therapeutic agents that target CSCs.

Hep3B 간암세포에서 개똥쑥 추출물에 의한 Cell Cycle Arrest 효과 (Cell Cycle Arrest Effects by Artemisia annua Linné in Hep3B Liver Cancer Cell)

  • 김은지;김근태;김보민;임은경;김상용;하성호;김영민;유제근
    • KSBB Journal
    • /
    • 제30권4호
    • /
    • pp.175-181
    • /
    • 2015
  • Cells proliferate via repeating process that growth and division. This process is G1, S, G2 and M four phases consists. Monitoring the progression of the cell cycle is a specific step that to be a continuous process is repeated to adjust the start of the next step. At this time, this process is called a Checkpoint. Currently, there are three known checkpoints that G1-S phase, G2-M phase, and the M phase. In this study, we confirmed that cell cycle arrest effects by ethanol extracts of Artemisia annua Linne (AAE) in Hep3B liver cancer cells. AAE was regulated proteins which involved in cell cycle such as pAkt, pMDM2, p53, p21, pCDK2 (T14/Y15). AAE induced cell cycle arrest in G1 checkpoint through phosphorylation of CDK2. Akt and p53 upstream is inhibited by AAE and p53 activated by non-activated pMDM2, p53 inhibitor. Thereby, activated p53 is transcript to p21 and activated p21 protein is combined with Cyclin E-pCDK2 complex. Therefore, we confirmed that AAE-induced cell cycle arrest was occurred by p21-Cyclin E-pCDK2 complex by inhibition of pAkt signal. Because of this cell cycle can't pass to S phase from G1 phase.

Cordycepin inhibits lipopolysaccharide-induced cell migration and invasion in human colorectal carcinoma HCT-116 cells through down-regulation of prostaglandin E2 receptor EP4

  • Jeong, Jin-Woo;Park, Cheol;Cha, Hee-Jae;Hong, Su Hyun;Park, Shin-Hyung;Kim, Gi-Young;Kim, Woo Jean;Kim, Cheol Hong;Song, Kyoung Seob;Choi, Yung Hyun
    • BMB Reports
    • /
    • 제51권10호
    • /
    • pp.532-537
    • /
    • 2018
  • Prostaglandin $E_2$ ($PGE_2$), a major product of cyclooxygenase-2 (COX-2), plays an important role in the carcinogenesis of many solid tumors, including colorectal cancer. Because $PGE_2$ functions by signaling through $PGE_2$ receptors (EPs), which regulate tumor cell growth, invasion, and migration, there has been a growing amount of interest in the therapeutic potential of targeting EPs. In the present study, we investigated the role of EP4 on the effectiveness of cordycepin in inhibiting the migration and invasion of HCT116 human colorectal carcinoma cells. Our data indicate that cordycepin suppressed lipopolysaccharide (LPS)-enhanced cell migration and invasion through the inactivation of matrix metalloproteinase (MMP)-9 as well as the down-regulation of COX-2 expression and $PGE_2$ production. These events were shown to be associated with the inactivation of EP4 and activation of AMP-activated protein kinase (AMPK). Moreover, the EP4 antagonist AH23848 prevented LPS-induced MMP-9 expression and cell invasion in HCT116 cells. However, the AMPK inhibitor, compound C, as well as AMPK knockdown via siRNA, attenuated the cordycepin-induced inhibition of EP4 expression. Cordycepin treatment also reduced the activation of CREB. These findings indicate that cordycepin suppresses the migration and invasion of HCT116 cells through modulating EP4 expression and the AMPK-CREB signaling pathway. Therefore, cordycepin has the potential to serve as a potent anti-cancer agent in therapeutic strategies against colorectal cancer metastasis.

Expression of the Proto-oncogene Pokemon in Colorectal Cancer - Inhibitory Effects of an siRNA

  • Zhao, Gan-Ting;Yang, Li-Juan;Li, Xi-Xia;Cui, Hui-Lin;Guo, Rui
    • Asian Pacific Journal of Cancer Prevention
    • /
    • 제14권9호
    • /
    • pp.4999-5005
    • /
    • 2013
  • Objective: This study aimed to investigate expression of the proto-oncogene POK erythroid myeloid ontogenic factor (Pokemon) in colorectal cancer (CRC), and assess inhibitory effects of a small interference RNA (siRNA) expression vector in SW480 and SW620 cells. Methods: Semi-quantitative reverse transcription-polymerase chain reaction (PCR) and immunohistochemistry were performed to determine mRNA and protein expression levels of Pokemon in CRC tissues. Indirect immunofluorescence staining was applied to investigate the location of Pokemon in SW480 and SW620 cells. The siRNA expression vectors that were constructed to express a short hairpin RNA against Pokemon were transfected to the SW480 and SW620 cells with a liposome. Expression levels of Pokemon mRNA and protein were examined by real-time quantitative-fluorescent PCR and western blot analysis. The effects of Pokemon silencing on proliferation of SW480 and SW620 cells were evaluated with reference to growth curves with MTT assays. Results: The mRNA expression level of Pokemon in tumor tissues ($0.845{\pm}0.344$) was significantly higher than that in adjacent tumor specimens ($0.321{\pm}0.197$). The positive expression ratio of Pokemon protein in CRC (87.0%) was significantly higher than that in the adjacent tissues (19.6%). Strong fluorescence staining of Pokemon protein was observed in the cytoplasm of the SW480 and SW620 cells. The inhibition ratios of Pokemon mRNA and protein in the SW480 cells were 83.1% and 73.5% at 48 and 72 h, respectively, compared with those of the negative control cells with the siRNA. In the SW620 cells, the inhibition ratios of Pokemon mRNA and protein were 76.3% and 68.7% at 48 and 72 h, respectively. MTT showed that Pokemon gene silencing inhibited the proliferation of SW480 and SW620 cells. Conclusion: Overexpression of Pokemon in CRC may have a function in carcinogenesis and progression. siRNA expression vectors could effectively inhibit mRNA and protein expression of Pokemon in SW480 and SW620 cells, thereby reducing malignant cell proliferation.

식물성 오메가-3계 지방산 급원인 아마씨 및 들깨의 항돌연변이 및 암세포 증식 억제 효과 (Inhibitory Effect of Linum usitatissimum and Perilla frutescens as Sources of Omega-3 Fatty Acids on Mutagenicity and Growth of Human Cancer Cell Lines)

  • 임선영
    • 생명과학회지
    • /
    • 제19권12호
    • /
    • pp.1737-1742
    • /
    • 2009
  • 본 연구에서는 식물 종자들 중에서 특히 $\alpha$-linolenic acid의 급원으로 대표적인 아마씨와 들깨를 중심으로 Ames 실험을 이용한 돌연변이 유발 및 인체 암세포 증식 억제 효과에 대해 비교 검토하였다. 간접돌연변이 $AFB_1$ (0.7 mg/plate)에 대해 들깨 메탄올 추출물은 농도의 증가와 더불어 돌연변이 억제효과가 증가하였다. 첨가농도 2.5 및 5 mg/plate일 때 각각 86% 및 94%의 돌연변이 억제 효과를 나타내었다. 아마씨 메탄올 추출물의 경우도 첨가농도 2.5 및 5 mg/plate일 때 각각 74% 및 75%의 항돌연변이 효과를 보였다. 직접 돌연변이인 MNNG (0.6 mg/plate)에 대한 들깨 및 아마씨 메탄올 추출물의 항돌연변이성 실험을 한 결과, 첨가농도 1.25 mg/plate일 때부터 활성이 나타나 5 mg/plate 일 때는 각각 78, 63%의 돌연변이 억제 효과를 나타내었다. S. typhimurium TA100 균주에 대한 $AFB_1$과 MNNG의 돌연변이 유발실험에서 두 가지 종자인 들깨와 아마씨는 직접돌연변이원에 대해서보다는 간접돌연변이원에 의해 유발된 돌연변이 저해에 더 효과적이었으며 들깨에 의한 항돌연변이 효과가 더 우수하였음을 관찰할 수가 있었다. 한편, 아마씨 메탄올 추출물을 0.5, 1, 2 mg/ml의 농도별로 인체 위암세포(AGS)에 처리했을 때 농도 의존적으로 암세포 증식 억제 효과가 증가하여 1 mg/ml 첨가농도에서 64%의 암세포 성장 억제 효과를 보였고, 2 mg/ml 농도에서 79%의 높은 암세포 증식 억제 효과를 나타내었다. 들깨 메탄올 추출물의 경우도 아마씨 메탄올 추출물과 유사하게 농도의존적으로 암세포의 증식을 억제시켰으며 첨가농도 2 mg/ml일 때 68%의 증식 억제효과를 살펴 볼 수가 있었다. 인체 결장암세포(HT-29)의 경우, AGS 세포에 처리했을 때처럼 아마씨 메탄올 추출물은 첨가농도 0.5 mg/ml에서부터 활성을 타나내어 첨가농도 2 mg/ml에서는 72%의 암세포 증식 억제효과를 나타내었다. 들깨 메탄올 추출물의 경우 첨가농도 0.5 mg/ml에서는 43%의 억제효과를 나타내었으나 첨가농도 2 mg/ml에서는 64%로 결장암세포의 증식을 억제시켰다. 인체 간암세포(Hep 3B)에 의한 증식 억제효과는 이상의 암세포에 대한 효과보다 다소 낮았으나 아마씨 및 들깨 메탄올 추출물은 첨가농도 2 mg/ml에서 각각 65% 및 59%의 저해효과를 나타내었다.

TIMP-2 유전자 재조합 아데노바이러스의 폐암세포 침윤 억제 효과 (TIMP-2 Gene Transfer Via Adenovirus Inhibits the Invasion of Lung Cancer Cell)

  • 오연목;이재호;유철규;정회순;김영환;한성구;심영수;이춘택
    • Tuberculosis and Respiratory Diseases
    • /
    • 제49권2호
    • /
    • pp.189-197
    • /
    • 2000
  • 연구배경 : 폐암은 진단 당시 이미 국소 침윤이나 원격 전이가 된 경우가 많고 이에 대한 적절한 치료법이 없기 때문에 예후가 불량하다. TIMP(tissue inhibitor of metalloproteinase)는 암세포의 침윤 및 전이에 중요한 역할을 하는 metalloproteinase를 억제하는 물질로서 생체 내에 존재하는 전이 억제 물질이다. 본 연구는 아데노바이러스를 이용한 TIMP 유전자 치료법을 개발하여 폐암의 치료에 응용하고자 하였다. 방법 : 폐암세포는 침윤 및 전이 능력이 큰 Calu-6를 사용하였다. TIMP-2 유전자를 pACCMVpLpA에 subcloning 한 후 pJM17과 함께 293 cell에 cotransfection 한 후 homologous recombination을 이용하여 Ad-TIMP-2를 제작하였다. Ad-TIMP-2를 Calu-6 cell에 이입하여 TIMP-2 protein 이 생산되는지를 TIMP-2 ELISA를 이용하여 확인하였고 TIMP-2의 생물학적 활성은 zymography로 확인하였다. Soft agar clonogenic assay로 종양형성능을 평가하였다. Ad-TIMP-2로 처리한 calu-6를 6주간 soft agar에서 키운 후 육안으로 보이는 colony 수를 측정하였다. Matrigel을 이용하여 invasion assay를 시행하여 calu-6의 침윤 능력의 변화를 평가하였다. 결과 : TIMP-2 ELISA 결과, 모세포 calu-6와 Ad-$\beta$-gal 이입 calu-6 그리고 Ad-TIMP-2 이입 calu-6는 각각 0.44, 0.43, 20.7 ${\mu}g/10^6$ cells/72hrs의 TIMP-2를 생산하였다. Zymography 결과 Ad-TIMP-2에 의해 생산된 TIMP-2는 matrix metalloproteinase-2의 gelatin 분해 효과를 억제하여 생물학적 활성을 확인할 수 있었다. Soft agar clonogenic assay 결과, 모세포인 calu-6는 453$\pm$53개, Ad-$\beta$gal과 Ad-TIMP-2 이입된 calu-6는 각각 332$\pm$35, 280$\pm$45개의 colony가 형성되어 유의한 감소를 보이지 못했다. Invasion assay 로 모세포 calu-6 에 대한 침윤율을 평가한 결과, Ad-$\beta$gal과 Ad-TIMP-2가 이입된 calu-6(10moi)는 각각 71$\pm$8.9%, 12$\pm$8.4%의 침윤율을 보였으며 $\beta$-gal 군에 비해 TIMP-2군이 유의하게 침윤율이 낮았다. 결론 : Ad-TIMP-2는 폐암 세포의 종양형성능을 억제하지 못하였으나 침윤은 억제하여 TIMP-2가 폐암 유전자 요법에 이용될 가능성을 제시해 주었다.

  • PDF