• Title/Summary/Keyword: tumor inhibition

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Trans-10, cis-12 Conjugated Linoleic Acid Modulates Nuclear Factor-${\kappa}B$ p65 Activity on the Production of Tumor Necrosis Factor-${\alpha}$ in Porcine Peripheral Blood Mononuclear Cells (돼지 말초혈액 단핵구세포에서 trans-10, cis-12 conjugated linoleic acid의 TNF-${\alpha}$ 생산에 대한 nuclear factor-${\kappa}B$ p65 활성 조절 효과)

  • Kim, Young-Beum;Lee, Ill-Woo;Kang, Ji-Houn;Yang, Mban-Pyo
    • Journal of Veterinary Clinics
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    • v.28 no.2
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    • pp.190-195
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    • 2011
  • Nuclear factor ${\kappa}B$ (NF-${\kappa}B$) is a nuclear transcription factor that modulates the expression of inflammatory cytokines such as tumor necrosis factor (TNF)-${\alpha}$. trans-10, cis-12 (t10c12)-conjugated linoleic acid (CLA) participates in the inhibition of TNF-${\alpha}$ production upon lipopolysaccharide (LPS)-stimulation. However, in our previous study, t10c12-CLA enhanced the production of TNF-${\alpha}$ by LPS-unstimulated porcine peripheral blood mononuclear cells (PBMCs) and RAW 264.7 macrophages in vitro. To resolve this apparent contradiction, we hypothesized that the effect of t10c12-CLA on TNF-${\alpha}$ production depends on NF-${\kappa}B$ activation induced by LPS stimulation. To test this hypothesis, we assessed the in vitro effect of t10c12-CLA on TNF-${\alpha}$ production and NF-${\kappa}B$ p65 activity in LPS-stimulated and LPS-unstimulated porcine PBMCs. t10c12-CLA treatment resulted in increased TNF-${\alpha}$ production by LPS-unstimulated PBMCs but decreased TNF-${\alpha}$ production by LPS-stimulated PBMCs. t10c12-CLA increased the degradation of inhibitory ${\kappa}B$ ($I{\kappa}B$)-${\alpha}$ protein and activated NF-${\kappa}B$ p65 in LPS-unstimulated PBMCs, but had the opposite effect in LPS-stimulated PBMCs. Notably, t10c12-CLA enhanced NF-${\kappa}B$ p65 binding activity in LPS-unstimulated PBMCs exposed to caffeic acid phenethyl ester (CAPE), a NF-${\kappa}B$ inhibitor. Conversely, it inhibited NF-${\kappa}B$ p65 binding activity in LPS-stimulated PBMCs exposed to CAPE. These results suggest that t10c12-CLA may have different actions under different physiological conditions, and that its effect may be associated with a change in NF-${\kappa}B$ p65 activity.

Regulatory Effect of Inflammatory Cytokines Secretion and Hypoxia-inducible $Factor-1{\alpha}$ Activation by Panax ginseng (인삼의 염증성 사이토카인 분비 및 저산소 유도인자-1${\alpha}$ 활성화 조절 효과)

  • Zo, Chul-Won;Lee, Seung-Hee;Kim, Dong-Woung;Lee, Seong-Kyun;Song, Bong-Keun
    • The Journal of Internal Korean Medicine
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    • v.27 no.4
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    • pp.864-878
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    • 2006
  • Purpose : Panax ginseng(PG) is considered to have salutary effects and stimulant actions on physical capacity. However, the effects of PG on the inflammatory cytokine secretion and hypoxia condition are still not understood. This study wasto elucidate the effect of PG on inflammatory cytokine secretion such as interleukin (IL)-1, IL-6, granulocyte macrophage colony stimulating factor (GM-CSF), and tumor necrosis factor $(TNF)-{\alpha}$. Also, the effects on the expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1 (HIF-1) were measured. Methods : The water extract of PG was administrated to HMC-1 cells before phorbol myristate acetate (PMA)+A23187 treatment. $IL-1{\beta}$, IL-6, $TNF-{\alpha}$, GM-CSF, and VEGF secretion were measured by a modified enzyme-linked immunosorbent assay (ELISA). HIF-1 activation was measured by transcription factor enzyme-linked immunoassay (TF-EIA) Results : PG significantly decreased secretion of $IL-1{\beta}$, IL-6, $TNF-{\alpha}$, and GM-CSF in PMA+A23187-induced HMC-1 cells. VEGF secretion was not changed but HIF-1 activation was decreased by the treatment of PG. Conclusions : PG inhibited the secretion of inflammatory cytokines, which impliesPG might contribute to treatment of mast cell-mediated inflammatory disease. Also, PG inhibited PMA+A23187-induced $HIF -1{\alpha}activation}$ and DNA-binding activity for HIF-1. Therefore, these data demonstrate that PG modulates inflammatory cytokines through inhibition of $HIF-1{\alpha}activation}$ activation.

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Drug Interaction between Ginseng Extract (GE) and Sorafenib (쏘라페닙과 홍삼추출물간의 약물상호작용)

  • Lee, Nam-Hee;Park, Ho-Jae;Rho, Ja-Sung;Kim, Mi-Kyung;Lee, Yu-Kyoung;Cho, Eun-A;Heo, Jeong;Cho, Mong;Hwang, Tae-Ho
    • Journal of Life Science
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    • v.21 no.11
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    • pp.1518-1525
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    • 2011
  • Sorafenib is the only approved systemic, therapeutic agent for hepatocellular carcinoma (HCC). The use of Ginseng Extract (GE) in cancer patients is growing worldwide; however, drug interaction between sorafenib and GE has not been illuminated. Four different human cancer cell lines including HepG2 were used and immunocompetent mice were implanted subcutaneously with a mouse HCC cell line. Treatment with low dose GE stimulated cell growth, while a high dose inhibited growth. pERK (phosphorylation of extracellular signal-regulated kinase) was concomitantly increased and decreased respective of different doses of GE. Antitumoral effect of sorafenib decreased in non-proliferating phase cells but was sensitized after low dose GE (LDG) treatment. PD98059 (ERK phosphorylation inhibitor) efficiently blocked ERK phosphorylation, resulting in loss of sorafenib sensitization even after LDG treatment. In the HCC mouse model, LDG alone slightly increased tumor size while sorafenib alone significantly decreased it. However, a combination of LDG and sorafenib significantly decreased tumor size compared with sorafenib alone. Increase of pERK was observed in some normal mice organs and mild inflammatory change was observed in some of these organs, suggesting pERK activation by LDG may cause unexpected toxicity in normal cells. GE, dose-dependently, induced stimulation or inhibition in some human cancer cell lines. Combinational use of GE and sorafenib possibly potentiated an antitumoral response to sorafenib. pERK level has been provided as a potential predictive marker for sorafenib. Our result may suggest GE's dual effects in relation to pERK level in HCC cancer cell lines, and that certain doses of GE can sensitize sorafenib.

Combined Treatment of Nonsteroidal Anti-inflammatory Drugs and Genistein Synergistically Induces Apoptosis via Induction of NAG-1 in Human Lung Adenocarcinoma A549 Cells (인간 A549 폐암세포에서 비스테로이드성 항염증제와 genistein의 복합처리에 의한 NAG-1 의존적 세포사멸 증진 효과)

  • Kim, Cho-Hee;Kim, Min-Young;Lee, Su-Yeon;Moon, Ji-Young;Han, Song-Iy;Park, Hye-Gyeong;Kang, Ho-Sung
    • Journal of Life Science
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    • v.19 no.8
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    • pp.1073-1080
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    • 2009
  • A number of studies have demonstrated that the regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) can reduce the risks of colorectal, oesophageal and lung cancers. NSAIDs have been shown to exert their anti-cancer effects through inducing apoptosis in cancer cells. The susceptibility of tumor cells to anti-tumor drug-induced apoptosis appears to depend on the balance between pro-apoptotic and anti-apoptotic programs such as nuclear factor kB (NF-kB), phosphatidylinositol 3-kinase (PI3K)-Akt/protein kinase B (PKB) and MEK1/2-ERK1/2 pathways. We examined the effects of pro-survival PI3K and ERK1/2 signal pathways on cell cycle arrest and apoptosis in response to NSAIDs including sulindac sulfide and NS398. We show that simultaneous inhibition of the Akt/PKB and ERK1/2 signal cascades could synergistically enhance the potential pro-apoptotic activities of sulindac sulfide and NS398. Similar enhancement was observed in cells treated with sulindac sulfide or NS398 and 100 ${\mu}$M genistein, an inhibitor of receptor tyrosine kinases (RTKs) that are upstream of PI3K and MEK1/2 signaling. We further demonstrate that NAG-1 is induced and plays a critical role(s) in apoptosis by NSAIDs-based combined treatment. In sum, our results show that combinatorialtreatment of sulindac sulfide or NS398 and genistein results in a highlysynergistic induction of apoptotic cell death to increase the chemopreventive effects of the NSAIDs, sulindac sulfide and NS398.

Induction of Apoptosis by Piceatannol in YD-15 Human Oral Cancer Cells (피세아타놀에 의한 YD-15 구강암세포의 세포자가사멸 유도 효과)

  • Lee, Hae-Nim;Jang, Hye-Yeon;Kim, Hyeong-Jin;Shin, Seong-Ah;Choo, Gang-Sik;Park, Byung-Kwon;Kim, Byeong-Soo;Jung, Ji-Youn
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.44 no.7
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    • pp.975-982
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    • 2015
  • Piceatannol (trans-3,4,3',5'-trihydroxystilbene), a natural stilbene, is an analogue of resveratrol. In the present study, possible mechanisms by which piceatannol exerts its pro-apoptotic action in cultured human oral cancer YD-15 cells were investigated. To investigate whether or not piceatannol has effects on cancer cell viability, human oral YD-15 cells were treated with piceatannol (0, 50, and $100{\mu}M$). Piceatannol treatment ($100{\mu}M$) showed the strongest inhibition of cell proliferation and reduced cell viability in a dose-dependent manner. Chromatin condensation detected by DAPI staining significantly increased in a concentration-dependent manner, indicating apoptosis. Piceatannol treatment activated initiator Bax (pro-apoptotic) and cPARP in a concentration-dependent manner. Further, piceatannol induced down-regulation of Bcl-2 (anti-apoptotic). We also evaluated the activity of piceatannol against oral cavity cancer tumors in mice. Piceatannol-treated nude mice bearing YD-15 xenograft tumors exhibited significantly reduced tumor volume and weight due to the potent effect of piceatannol on tumor cell apoptosis, as determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay. Immunohistochemistry staining showed elevated expression of cleaved-caspase-3 as well as reduced expression of Ki-67 in the piceatannol-treated group. Therefore, piceatannol can be developed as a cancer preventive medicine due to its growth inhibitory effects and induction of apoptosis in human oral cancer cells.

Immunomodulatory and Anti-Inflammatory Activity of Mulberry (Morus alba) Leaves Fermented with Hericium erinaceum Mycelium by Solid-State Culture (Solid-State Culture를 이용하여 조제한 노루궁뎅이버섯 균사체-뽕잎발효물의 면역 및 항염증 활성)

  • Kim, Hoon;Jeong, Jae-Hyun;Shin, Ji-Young;Kim, Dong-Goo;Yu, Kwang-Won
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.40 no.9
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    • pp.1333-1339
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    • 2011
  • After mulberry (Morus alba) leaves were fermented with Hericium erinaceum mycelium by solid-state culture to enhance physiological activity, fermented mulberry leaves (MA-HE) was extracted by hot-water (MA-HEHW) and ethanol (MA-HE-E). MA-HE-HW showed enhanced mitogenic and intestinal immune system modulating activities (1.41 and 1.52 fold of saline control, respectively) compared to hot-water extracts of non-fermented mulberry leaves (MA-HW) and H. erinaceum mycelium (HE-HW) at $100\;{\mu}g$/mL. Meanwhile, when we tested the inhibitory effects of extracts on nitric oxide (NO), tumor necrosis factor (TNF)-${\alpha}$, and interleukin (IL)-$1{\beta}$ and IL-6 production, MA-HE-E significantly inhibited these pro-inflammatory mediators in LPS-stimulated RAW 264.7 cells (45.1, 41.3, 70.2, and 55.7% inhibition of LPS control at $1,000\;{\mu}g$/mL). In addition, MA-HE-HW and MA-HE-E did not show any cytotoxicity on RAW 264.7 cells at $1,000\;{\mu}g$/mL whereas HE-E and MA-E indicated cytotoxicity (80.1 and 30.7% cell viability of saline control). These results suggest that mulberry leaves fermented with H. erinaceum by solid-state culture might have enhanced immunomodulatory and anti-inflammatory effects compared to non-fermented mulberry leaves, resulting in ingredients biotransformed for fermentation with H. erinaceum mycelium.

Enhanced Growth Inhibition by Combined Gene Transfer of p53 and $p16^{INK4a}$ in Adenoviral Vectors to Lung Cancer Cell Lines (폐암세포주에 대한 p53 및 $p16^{INK4a}$의 복합종양억제유전자요법의 효과)

  • Choi, Seung -Ho;Park, Kyung-Ho;Seol, Ja-Young;Yoo, Chul-Gyu;Lee, Choon-Taek;Kim, Young-Whan;Han, Sung-Koo;Shim, Young-Soo
    • Tuberculosis and Respiratory Diseases
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    • v.50 no.1
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    • pp.67-75
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    • 2001
  • Background : Two tumor suppressor genes, p53 and p16, which have different roles in controlling the cell cycle and inducing apoptosis, are frequently inactivated during carcinogenesis including lung cancer. Single tumor suppressor gene therapies using either with p53 or p16 have been studied extensively. However, there is a paucity of reports regarding a combined gene therapy using these two genes. Methods : The combined effect of p53 and p16 gene transfer by the adenoviral vector on the growth of lung cancer cell lines and its interactive mechanism was investigated. Results : An isobologram showed that the co-transduction of p53 and p16 exhibited a synergistic growth in hibitory effect on NCI H358 and an additive effect on NCI H23. Cell cycle analysis demonstrated the induction of a synergistic G1/S arrest by a combined p53 and p16 transfer. This synergistic interaction was again confirmed in a soft agar confirmed in a soft agar clonogenic assay. Conclusion : These observations suggest the potential of a p53 and p16 combination gene therapy as another potent strategy in cancer gene therapy.

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Antimutagenicity and Cytotoxic Effects of Methanol Extract from Deep Sea Water Salt and Sea Tangle Added Soybean Paste (Doenjang) (해양심층수염 및 다시마분말을 첨가한 개량식 된장의 항돌연변이원성 및 암세포성장억제에 미치는 영향)

  • Ham, Seung-Shi;Kim, Soo-Hyun;Yoo, Su-Jong;Oh, Hyun-Taek;Choi, Hyun-Jin;Chung, Mi-Ja
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.37 no.4
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    • pp.416-421
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    • 2008
  • This study was performed to determine the antimutagenic and anticytotoxic effects of soybean paste (doenjang) added deep sea water salt and see tangle in Salmonella Typhimurium TA98, TA100 and human cancer cell lines. In the Ames test, methanol extract of doenjang did not exhibit any mutagenicity but showed substantial inhibitory effects against mutation induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and 4-nitroquinoline-1-oxide (4NQO). The methanol extracts of doenjang ($200{\mu}g$/plate) added deep sea salt and see tangle (doenjang C) showed approximately 89.1% and 70% inhibitory effect on the mutagenesis induced by MNNG and 4NQO against TA100 strain, whereas 84.4% inhibitions were observed on the mutagenesis induced by 4NQO against TA98 strain. The cytotoxic effects of doenjang methanol extracts against the cell lines with human cervical adenocarcinoma (HeLa), human hepatocellular carcinoma (Hep3B), human gastric carcinoma (AGS), human lung carcinoma (A549) and human breast adenocarcinoma (MCF-7) were inhibited with the increase of the extract concentration. The treatment of 1.0 mg/mL doenjang C of methanol extracts showed strong cytotoxicities of 71%, 74.4%, 66.2%, 77.3%, and 71.2% against HeLa, Hep3B, AGS, A549, and MCF-7, respectively. In contrast 1 mg/mL treatment of doenjang C methanol extracts had only $10{\sim}40%$ cytotoxicity on normal human embryonal kidney cell (293). Doenjang methanol extract inhibited significantly the tumor growth in mice injected sarcoma-180 cells. Especially, doenjang C methanol extract showed an inhibition of tumor cell activity of 33% by the administration of 25 mg/kg methanol extracts.

Anti-inflammation effect of blueberry (Vaccinium ashei) leaf extract on RAW 264.7 macrophages stimulated by lipopolysaccharide (Lipopolysaccharide에 의해 활성화된 RAW 264.7대식세포에서 블루베리 잎(Vaccinium ashei) 추출물의 항염증 효과)

  • Kim, Dong In;Kim, Hyun Jung;Yun, Jong Moon;Lee, Ji Hye;Han, So Jung;Kim, Ha Eun;Jang, Min Jung;An, Bong Jeun
    • Food Science and Preservation
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    • v.25 no.1
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    • pp.107-116
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    • 2018
  • The aim of this study is to investigate the antioxidant and intracellular anti-inflammatory efficacy of blueberry leaf extracted with hot water (BLW), 70% ethanol (BLE), and 70% acetone (BLA) in RAW 264.7 macrophages. In order to evaluate the anti-inflammatory effect of blueberry leaf extracts, RAW 264.7 macrophages were stimulated with lipopolysaccharide (LPS) to induce the production of inflammation-related factors, which were measure by Western blotting and real-time PCR methods. i-NOS, COX-2 protein, and mRNA expression showed concentration-dependent decrease. The decreases in the mRNA expression levels of interleukin-$1{\beta}$ (IL-$1{\beta}$), interleukin-6 (IL-6), tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), and prostaglandin $E_2$ ($PGE_2$) were concentration-dependent. Further, the antioxidant effects of blueberry leaf on total polyphenol contents, electron donating ability and $ABTS^+$ radical scavenging activity were evaluated. The total polyphenol contents of BLW, BLE, and BLA were $217.04{\pm}2.98$, $156.72{\pm}3.90$, and $182.88{\pm}3.02mg\;TAE/g$, respectively, while the electron donating abilities at $1,000{\mu}g/mL$ of BLW, BLE, and BLA were 81.7, 79.6, and 79.3%, respectively. The $ABTS^+$ radical scavenging activity was fond to be concentration dependent. The nitric oxide (NO) production inhibition activities at $50{\mu}g/mL$ of BLW, BLE, and BLA were 35.1, 42.4 and 42.7%, respectively. In conclusion, the antioxidant and anti-inflammatory test results indicate that blueberry leaf extracts (BLW, BLE, and BLA) can be used as potential anti-inflammatory agents.

Pathophysiological Regulation of Vascular Smooth Muscle Cells by Prostaglandin F2α-dependent Activation of Phospholipase C-β3 (Prostaglandin F2α 의존적 phospholipase C-β3 활성화에 의한 혈관평활근세포의 병태생리 조절 연구)

  • Kang, Ki Ung;Oh, Jun Young;Lee, Yun Ha;Lee, Hye Sun;Jin, Seo Yeon;Bae, Sun Sik
    • Journal of Life Science
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    • v.28 no.12
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    • pp.1516-1522
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    • 2018
  • Atherosclerosis is an obstructive vessel disease mainly caused by chronic arterial inflammation to which the proliferation and migration of vascular smooth muscle cells (VSMCs) is the main pathological response. In the present study, the primary responsible inflammatory cytokine and its signaling pathway was investigated. The proliferation and migration of VSMCs was significantly enhanced by the prostaglandin $F_{2{\alpha}}$ ($PGF_{2{\alpha}}$), while neither was affected by tumor necrosis factor ${\alpha}$. Prostacyclin $I_2$ was seen to enhance the proliferation of VSMCs while simultaneously suppressing their migration. Both prostaglandin $D_2$ and prostaglandin $E_2$ significantly enhanced the migration of VSMCs, however, proliferation was not affected by either of them. The proliferation and migration of VSMCs stimulated by $PGF_{2{\alpha}}$ progressed in a dose-dependent manner; the $EC_{50}$ value of both proliferation and migration was $0.1{\mu}M$. VSMCs highly expressed the phospholipase isoform $C-{\beta}3$ ($PLC-{\beta}3$) while others such as $PLC-{\beta}1$, $PLC-{\beta}2$, and $PLC-{\beta}4$ were not expressed. Inhibition of the PLCs by U73122 completely blocked the $PGF_{2{\alpha}}$-induced migration of VSMCs, and, in addition, silencing $PLC-{\beta}3$ significantly diminished the $PGF_{2{\alpha}}$-induced proliferation and migration of VSMCs. Given these results, we suggest that $PGF_{2{\alpha}}$ plays a crucial role in the proliferation and migration of VSMCs, and activation of $PLC-{\beta}3$ could be involved in their $PGF_{2{\alpha}}$-dependent migration.