• Title/Summary/Keyword: tumor inhibition

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Effect of Xanthium sibiricum Patr. on Carcinogenesis in Human Cell Lines (창이자의 사람 세포주에서의 발암 억제효과)

  • So, Myung-Suk
    • Journal of Korean Biological Nursing Science
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    • v.12 no.3
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    • pp.127-132
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    • 2010
  • Purpose: The aim of this study is to evaluate the effect of Xanthium sibiricum Patr. on carcinogenesis. Method: Water extract from Xanthium sibiricum Patr. (XPW) was prepared and investigated for the potential antitumor activity and inhibition of benzo[a]pyrene-DNA adduct formation and free radical formation. Result: It was shown that the water possess considerable toxicity toward tumor cell lines. Concentration of XPW at 1.0 mg/mL and 2.5 mg/mL resulted in more than 30% inhibition of growth in HeLa cells. Toxicity of XPW to A549 revealed that 54% inhibition of growth at concentration of 2.5 mg/mL. At concentrations of 0.5 mg/mL, 1.0 mg/mL and 2.5 mg/mL of XPW, the binding of [$^3H$]B[a]P metabolites to DNA of human Chang cell was inhibited by 19%, 33%, and 41%, respectively. There 18% and 32% inhibition in the free radical formation with XPW at the concentration of 1.0 mg/mL and 2.5 mg/mL, respectively. Conclusion: Water extract from Xanthium sibiricum Patr. (XPW) has antitumor and cancer chemopreventive activities.

Antitumor and Immunomodulatory Effects of Glycyrrhizae Radix Aqua-acupuncture Solution (감초 약침액의 항암 및 면역활성에 미치는 영향)

  • Park, Gyung-Mi;Cho, Kyoung-Hee;Shon, Yun-Hee;Lim, Jong-Kook;Nam, Kyung-Soo
    • Korean Journal of Pharmacognosy
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    • v.31 no.1
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    • pp.7-15
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    • 2000
  • Glycyrrhizae Radix aqua-acupuncture solution (GRAS) and Glycyrrhizae Radix water-extracted solution (GRWS) were prepared and tested for organ toxicities, antitumor activities, and immunomodulatory effects. The organ-toxicity of GRAS to male ICR mice was studied by the measurements of glutamic oxaloacetic transaminase (GOT), glutamic pyruvate transaminase (GPT), lactate dehydrogenase (LDH), and alkaline phosphatase (ALP-s) activities after injection of GRAS for 7 days. The activities of GOT, GPT, LDH, ALP-s were decreased with GRAS. It was shown to possess considerable toxicity toward various tumor cell lines. Concentration of GRAS at 1.5g/ml and 3g/ml resulted in more than 80% inhibition of growth in Ehrlich ascites tumor cells (EATC), Hepa1c1c7, and HeLa cells. Toxicity of GRAS to A549 revealed that 68% inhibition of growth. GRWS at the concentration of 3g/ml showed more than 80% inhibition of growth with EATC, Hepalclc7, A549 and HeLa. In morphological study, the number of cells were decreased, and the shape of cells was round-form in EATC, Hepalclc7, A549 and HeLa cells with GRAS. Administration of GRAS inhibited the growth of EATC in vivo. Mice given EATC at 1.5g/ml or 0.3g/ml GRAS had 16.7% to 50% survival after 21 days. GRAS increased the proliferation of T and B cells and the cytolytic activity of purified T cell. The biosyntheses of nucleic acid and protein of EATC, Hepalclc7, A549 and HeLa cells were inhibited by GRAS.

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Inhibition Effects of Lamellarin D on Human Leukemia K562 Cell Proliferation and Underlying Mechanisms

  • Zhang, Nan;Wang, Dong;Zhu, Yu;Wang, Jian;Lin, Hong
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.22
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    • pp.9915-9919
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    • 2014
  • Lamellarin D (LamD) is a marine alkaloid with a pronounced cytotoxicity against a large panel of cancer cells, affecting cell growth and inducing apoptosis. However, the molecular mechanisms of action of this compound are poorly understood. In this study, the anticancer efficacy of LamD was investigated in human leukemia K562 cells. The results showed suppressed cell proliferation and induction of G0/G1-phase arrest,while expression of CDK1, and activity of smad3 and smad5 were reduced, but that of p27, p53 and STGC3 was increased. LamD induced cell apoptosis through activation of caspases-8/-3, inhibition of survivin and Bcl-2, suggesting that this compound may also act through a caspase-independent pathway. Moreover, LamD inhibited the secretion of TGF-${\beta}$, IL-$1{\beta}$, IL-6, IL-8 and other inflammatory cytokines and the transcriptional activity of transcription factor NF-${\kappa}B$ in human leukemia K562 cells.Taken together, our results suggest that LamD-mediated inhibition of leukemia cell proliferation may be related to the induction of apoptosis and the regulation of cell cycle, tumor-related gene expression and cytokine expression, which may provide a new way of thinking for the treatment leukemia.

5-Aminoisoquinolinone Reduces the Expression of Vascular Endothelial Growth Factor-C via the Nuclear Factor-kappa B Signaling Pathway in CT26 Cells

  • Wu, Wei-Qiang;Fauzee, Nilufer Jasmine Selimah;Wang, Ya-Lan
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.3
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    • pp.991-994
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    • 2012
  • Objective: VEGF-C has recently been identified as a key molecule which is involved in tumor lymphangiogenesis. The aim of this research was to investigate the role of PARP-1 inhibition in the regulation of VEGF-C expression in CT26 cells. Methods: CT26 cells were treated with or without the PARP-1 inhibitor 5-aminoisoquinolinone (5-AIQ). The expression of PARP-1, NF-kB, and VEGF-C proteins in CT26 cells was measured by Western blot analysis and the VEGF-C mRNA level was determined by reverse transcription polymerase chain reaction (RT-PCR). CT26-secreted VEGF-C was detected by enzyme-linked immunosorbent assay (ELISA). Results: The results of Western blot analysis showed that the expression levels of PARP-1, NF-kB, and VEGF-C were reduced in 5-AIQ treated CT26 cells and the levels of VEGF-C mRNA in 5-AIQ treated CT26 were significantly lower than t in 5-AIQ-untreated cells (P<0.05). The concentrations of CT26-secreted VEGF-C were also dramatically decreased (P<0.05). Conclusion: Here, we provide evidence for the first time that PARP-1 inhibition dramatically reduces VEGF-C expression via the nuclear factor NF-kB signaling pathway. We therefore propose that PARP-1 inhibition has an anti-lymphangiogenic effect and may contribute to the prevention of metastatic dissemination via the lymphatic system.

The proteasome inhibition enhances apoptosis by P53 expression and the dissipation of mitochondrial transmembrane potential in TRAIL-resistant lung cancer cells (Proteasome 억제에 의한 P53의 발현과 미토콘드리아 막 전압의 소실로 TRAIL에 저항하는 폐암세포의 사멸 강화)

  • Seol, Jae-Won;Park, Sang-Youel
    • Korean Journal of Veterinary Research
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    • v.49 no.1
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    • pp.1-8
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    • 2009
  • The ubiquitin-proteasome mediated protein degradation pathway plays an important role in regulating both cell proliferation and cell death. Proteasome inhibitors are well known to induce apoptosis in various human cancer cell lines. We investigated the effect of combined treatment with proteasome inhibitor and TRAIL, and a possible mechanism of the enhancing apoptosis by the both treatment, on TRAIL-resistant non-small cell lung cancer. A549 cells were exposed to the N-Acetyl-Leu-Leu-Norleu-al (ALLN) as a proteasome inhibitor and then treated with recombinant TRAIL protein. In A549 cells under proteasome inhibition conditions by pretreatment with ALLN, TRAIL treatment significantly decreased cell viability compared to that ALLN and TRAIL alone treatment. Also, the both treatment induced cell damage through DNA fragmentation and p53 expression. In addition, the combined treatment of both markedly increased caspase-8 activation, especially the exposure for 2 h, and Bax expression and induced the dissipation of mitochondrial transmembrane potential in A549 cells. Taken together, these findings showed that proteasome inhibition by ALLN enhanced TRAIL-induced apoptosis via DNA degradation by activated P53 and mitochondrial transmembrane potential loss by caspase-8 activation and bax expression. Therefore, our results suggest that proteasome inhibitor may be used a very effectively chemotherapeutic agent for the tumor treatment, especially TRAIL-resistant tumor cell.

Antimicrobial Activities Against Oral Microbes and Growth-inhibitory Effect on Oral Tumor Cell by Extract of Paeonia lactiflora (작약 추출물의 구강병원균에 대한 항균성 및 구강암 세포 증식 억제효과)

  • Park, Hyun-Suk;Min, Kyung-Jin;Cha, Chun-Geun;Song, Jin-Wook;Son, Jin-Chang
    • Journal of Environmental Health Sciences
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    • v.33 no.1 s.94
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    • pp.21-29
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    • 2007
  • Paeonia lactiflora was stepwise extracted with hexane, chloroform, ethyl acetate, butanol and water. Anti-microbial activity of each extract was investigated. Methanol extract of P. lactiflora revealed anti-microbial activity against S. mutans, C. albicans, and S. aureus. Also, hexane fraction revealed anti-bacterial activity against S. mutans and ethyl acetate fraction acted as potent anti-microbial agent on C. albicans and S. aureus. The relative growth ratio(RGR) of hexane fraction of P. lactiflora against S. mutans were determined as 77.8% in concentration of 0.125 mg/ml, 98.46% in 0.25 mg/ml and 100% in 0.5 mg/ml. The ethyl acetate fraction of P. lactiflora revealed RGR against C. albicans as 52.5% in concentration of 0.125 mg/ml, 60.83% in 0.25 mg/ml and 78.33% in 0.5 mg/ml. It indicate that increasing concentration increase RGR. The measured minimal inhibitory concentration(MIC) of hexane fraction on S. mutans KCTC 5316 strain was 0.5 mg/ml and MIC of ethyl acetate fraction on C. albicans KCTC 7270 was 2.0 mg/ml. The experiment of inhibition to growth of KB roll(oral squamous cell carcinoma) result 61.9% in butanol, 76.7% in hexane extract of P. lactiflora. The hexane extract exhibit potent inhibition effect to the growth of KB cell. These results suggest that the hexane extract of Paeonia lactiflora has antimicrobial activity against S. mutans and has preventive effect to dental caries in addition to potent inhibition to KB cell growth.

Menin Enhances Androgen Receptor-Independent Proliferation and Migration of Prostate Cancer Cells

  • Kim, Taewan;Jeong, Kwanyoung;Kim, Eunji;Yoon, Kwanghyun;Choi, Jinmi;Park, Jae Hyeon;Kim, Jae-Hwan;Kim, Hyung Sik;Youn, Hong-Duk;Cho, Eun-Jung
    • Molecules and Cells
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    • v.45 no.4
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    • pp.202-215
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    • 2022
  • The androgen receptor (AR) is an important therapeutic target for treating prostate cancer (PCa). Moreover, there is an increasing need for understanding the AR-independent progression of tumor cells such as neuroendocrine prostate cancer (NEPC). Menin, which is encoded by multiple endocrine neoplasia type 1 (MEN1), serves as a direct link between AR and the mixed-lineage leukemia (MLL) complex in PCa development by activating AR target genes through histone H3 lysine 4 methylation. Although menin is a critical component of AR signaling, its tumorigenic role in AR-independent PCa cells remains unknown. Here, we compared the role of menin in AR-positive and AR-negative PCa cells via RNAi-mediated or pharmacological inhibition of menin. We demonstrated that menin was involved in tumor cell growth and metastasis in PCa cells with low or deficient levels of AR. The inhibition of menin significantly diminished the growth of PCa cells and induced apoptosis, regardless of the presence of AR. Additionally, transcriptome analysis showed that the expression of many metastasis-associated genes was perturbed by menin inhibition in AR-negative DU145 cells. Furthermore, wound-healing assay results showed that menin promoted cell migration in AR-independent cellular contexts. Overall, these findings suggest a critical function of menin in tumorigenesis and provide a rationale for drug development against menin toward targeting high-risk metastatic PCa, especially those independent of AR.

Chelidonium majus Induces Apoptosis of Human Ovarian Cancer Cells via ATF3-Mediated Regulation of Foxo3a by Tip60

  • Shen, Lei;Lee, Soon;Joo, Jong Cheon;Hong, Eunmi;Cui, Zhen Yang;Jo, Eunbi;Park, Soo Jung;Jang, Hyun-Jin
    • Journal of Microbiology and Biotechnology
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    • v.32 no.4
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    • pp.493-503
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    • 2022
  • Forkhead transcription factor 3a (Foxo3a) is believed to be a tumor suppressor as its inactivation leads to cell transformation and tumor development. However, further investigation is required regarding the involvement of the activating transcription factor 3 (ATF3)-mediated Tat-interactive protein 60 (Tip60)/Foxo3a pathway in cancer cell apoptosis. This study demonstrated that Chelidonium majus upregulated the expression of ATF3 and Tip60 and promoted Foxo3a nuclear translocation, ultimately increasing the level of Bcl-2-associated X protein (Bax) protein. ATF3 overexpression stimulated Tip60 expression, while ATF3 inhibition by siRNA repressed Tip60 expression. Furthermore, siRNA-mediated Tip60 inhibition significantly promoted Foxo3a phosphorylation, leading to blockade of Foxo3a translocation into the nucleus. Thus, we were able to deduce that ATF3 mediates the regulation of Foxo3a by Tip60. Moreover, siRNA-mediated Foxo3a inhibition suppressed the expression of Bax and subsequent apoptosis. Taken together, our data demonstrate that Chelidonium majus induces SKOV-3 cell death by increasing ATF3 levels and its downstream proteins Tip60 and Foxo3a. This suggests a potential therapeutic role of Chelidonium majus against ovarian cancer.

Cytotoxic effects of ethanol extracts of Saussurea lappa mediated by mitochondrial apoptotic pathway

  • Koh Seung-Hee;Ko Seong-Gyu;Jun Chan-Yong;Park Chong-Hyeong
    • The Journal of Korean Medicine
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    • v.25 no.4
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    • pp.79-89
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    • 2004
  • Saussurea lappa and Taraxacum mongolicum have been used for herbal medicinal treatments against cancers in East Asia. We performed this study to understand the molecular basis underlying the anti-tumor effects of two herbs and analyzed the effects of these medicinal herbs on proliferation and on expression of cell growth/apoptosis related molecules by using an AGS gastric cancer cell line. The treatments of Saussurea lappa dramatically reduced cell viabilities in a dose and time-dependent manner, but Taraxacum mongolicum did not. FACS analysis and Annexin V staining assay also showed that Saussurea lappa induces apoptotic cell death of AGS. Expression analyses via RT-PCR and Western blots revealed that Saussurea lappa increased expression of the p53 and its downstream effector p21/sup Waf1/, and that the both increased expression of apoptosis related Bax and cleavage of active caspase-3 protein. We also confirmed the translocation of Bax to mitochondria Collectively, our data demonstrate that Saussurea lappa induces growth inhibition and apoptosis of human gastric cancer cells, and these effects are correlated with down- and up-regulation of growth-regulating apoptotic and tumor suppressor genes, respectively.

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The in vivo photothermal treatment of gold nanorod in the mouse ear model

  • Liu, Bruce Yao Wen;Chen, Cheng-Lung;Lee, Shin-Yu;Chang, Fu-Hsiung;Lin, Win-Li;Chia, Chih-Ta;Chen, Yang-Yuan
    • Biomaterials and Biomechanics in Bioengineering
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    • v.1 no.1
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    • pp.41-50
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    • 2014
  • Gold nanorod's exceptional light to heat transduction is a robust phonomenon that has been extensively verified. The phenomenon is a trait from which many novel applications across disciplines have been proposed. In this investigation, the feasibility of utilizing heat harvested from such photothermal method to combat cancer is presented. Using non-invasive laser methods, an in vivo study is conducted on mouse ear tumors administered with gold nanorods (Au NRs). An emphasis is placed on monitoring the tumor developments after photothermal treatments, over time. The findings reveal significant tumor growth surpression at a threshold laser power of $0.6W/cm^2$ lasting 2 minutes; this energy also brought about dramatic size reduction in treated tumors. Furthermore, the apparent formation of an eschar over the laser treated region indicates extensive hemorrhagic necrosis of the tumor tissue; a phenomenon implicative to the inhibition of angiogenesis.