• Title, Summary, Keyword: anti-tumor

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T Cell Stimulatory Effects of Korean Red Ginseng through Modulation of Myeloid-Derived Suppressor Cells

  • Jeon, Chan-Oh;Kang, Soo-Won;Park, Seung-Beom;Lim, Kyung-Taek;Hwang, Kwang-Woo;Min, Hye-Young
    • Journal of Ginseng Research
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    • v.35 no.4
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    • pp.462-470
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    • 2011
  • Myeloid-derived suppressor cells (MDSCs) actively suppress immune cells and have been considered as an impediment to successful cancer immunotherapy. Many approaches have been made to overcome such immunosuppressive factors and to exert effective anti-tumor effects, but the possibility of using medicinal plants for this purpose has been overlooked. Korean red ginseng (KRG) is widely known to possess a variety of pharmacological properties, including immunoboosting and anti-tumor activities. However, little has been done to assess the anti-tumor activity of KRG on MDSCs. Therefore, we examined the effects of KRG on MDSCs in tumor-bearing mice and evaluated immunostimulatory and anti-tumor activities of KRG through MDSC modulation. The data show that intraperitoneal administration of KRG compromises MDSC function and induces T cell proliferation and the secretion of IL-2 and IFN-${\gamma}$, while it does not exhibit direct cytotoxicity on tumor cells and reduced MDSC accumulation. MDSCs isolated from KRG-treated mice also express significantly lower levels of inducible nitric oxide synthase and IL-10 accompanied by a decrease in nitric oxide production compared with control. Taken together, the present study demonstrates that KRG enhances T cell function by inhibiting the immunosuppressive activity of MDSCs and suggests that although KRG alone does not exhibit direct anti-tumor effects, the use of KRG together with conventional chemo- or immunotherapy may provide better outcomes to cancer patients through MDSC modulation.

Comparative Antitumor Activity of Water Extracts from Fruiting Body of Phellinus linteus, Phellinus baumii and Phellinus gilvus (Phellinus linteus, Phellinus baumii 및 Phellinus gilvus 자실체 추출물의 항암효과 비교)

  • 배재성;황미현;장광호;이만휘;이근우;조우식;최성국;윤효인;임종환
    • Toxicological Research
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    • v.20 no.1
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    • pp.37-42
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    • 2004
  • This study was undertaken to investigate comparative anti-tumor activity of water extracts of Phellinus gilvus (PGE), Phellinus linteus (PLE), and Phellinus baumii (PBE) in vitro. The anti-tumor activity in the present study was evaluated by sulforhodamine B (SRB) and microtetrazolium (MTT) assay in terms of cell survival level. The tumor cells (sarcoma 180 and P388) were treated with PGE, PLE, and PBE (7.5, 15, and 30 $\mu\textrm{g}$/ml) and Doxorubicin (DOX) (0.001~10 $\mu\textrm{M}$). The results showed that DOX, PGE, and PLE inhibited proliferation showing a dose-dependent manner against both tumor cells. However, PBE was inhibited by the only 30 $\mu\textrm{g}$/ml in both cells proliferation. In conclusion, all of PGE, PLE, and PBE used in this study have shown anti-tumor activity against both sarcoma 180 and P388. Among them, PLE was the most effective in anti-tumor activity against sarcoma 180 (p<0.05) and PGE was against P388 in SRB assay. PLE, however, was against P388 (p<0.05) in MTT assay.

Enhanced Tumor-targeted Gene Delivery by Immunolipoplexes Conjugated with the Humanized Anti-TAG-72 Fab' Fragments

  • Kim, Keun-Sik;Park, Yong-Serk;Hong, Hyo-Jeong;Kim, Kwang-Pyo;Lee, Kwang-Hyun;Kim, Dong-Eun
    • Bulletin of the Korean Chemical Society
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    • v.33 no.2
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    • pp.651-656
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    • 2012
  • Cationic immunoliposomes were prepared by conjugation of Fab' fragments of the recombinant humanized monoclonal antibody (HuCC49) against tumor-associated glycoprotein (TAG)-72 to sterically unilamella liposomes. The cationic immunoliposomes are composed of cationic lipid (O,O'-dimyristyl-N-lysyl aspartate, DMKD), cholesterol, and 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[maleimide(polyethyleneglycol)$_{2000}$] (DPPE-PEG-maleimide) with a molar ratio of 0.5:0.47:0.03. Plasmid DNA was effectively condensed by addition of transferrin (Tf) during the formation of anti-TAG-72 PEG-immunolipoplexes (PILPs). These anti-TAG-72 PILPs were able to adhere to the surface of TAG-72-overexepressing LS174T human colon cancer cells more effectively than conventional liposomes, thereby facilitating gene delivery in vitro. Furthermore, intravenous administration of the anti-TAG-72 PILPs into the tumor-carrying mice exhibited efficient localization of the reporter gene in the tumor tissues.

Different Way of LMP/TAP/MHC Gene Clustering in Vertebrates,. Viviparity and Anti-tumor Immunity Failure

  • Bubanovic, Ivan;Najman, Stevo
    • Animal cells and systems
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    • v.9 no.1
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    • pp.1-7
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    • 2005
  • Class I and class II MHC genes have been identified in most of the jawed vertebrate taxa. In all investigated bony fish species, unlike mammals, the classical class I and class II MHC genes are not linked and even are found on different chromosomes. Linking and clustering of the class I and class II MHC genes is not the only phenomenon clearly detected in the evolution of immune system from cartilaginous to mammals. In all non-mammalian classes the LMP/TAP genes are highly conserved within class I genes region, while these genes are conserved within class II genes region only in mammals. Today we know that LMP/TAP genes in mammals have a crucial role in peptide processing for presentation within class I molecules, as well as in anti-tumor immunity. For these reasons, differences in clustering of LMP/TAP/MHC genes can be responsible for the differences in mechanisms and efficacy of anti-tumor immunity in non-mammalian vertebrates compared to same mechanisms in mammals. Also, the differences in cytokine network and anti-tumor antigens presentation within classes of vertebrates can be explained by toe peculiarity of LMP/TAP/MHC gene clustering.

Dealcoholized Korean Rice Wine (Makgeolli) Exerts Potent Anti-Tumor Effect in AGS Human Gastric Adenocarcinoma Cells and Tumor Xenograft Mice

  • Shin, Eun Ju;Kim, Sung Hee;Kim, Jae Ho;Ha, Jaeho;Hwang, Jin-Taek
    • Journal of Microbiology and Biotechnology
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    • v.25 no.9
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    • pp.1485-1492
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    • 2015
  • Makgeolli is a traditional wine in Korea and has been traditionally believed to exhibit health benefits. However, the inhibitory effect of dealcoholized makgeolli (MK) on cancer has never been investigated scientifically. In this study, MK exhibited an anti-angiogenic effect by inhibiting tube formation in human umbilical vein endothelial cells, without cytotoxicity. Treatment with MK reduced the proliferation of AGS human gastric adenocarcinoma cells in a dose-dependent manner and increased the sub-G1 population. Next, we evaluated whether MK could induce apoptosis in AGS cells by using the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay or Annexin V method. Treatment with MK at 500 and 1,000 μg/ml increased the number of TUNEL-positive AGS cells. Under the same conditions, MK-treated (500 and 1,000 μg/ml) cells showed significant induction of early or late apoptosis, compared with untreated cells (no induction). In addition, MK also induced phosphatase and tensin homolog (PTEN) expression in AGS cells. However, p53 expression in AGS cells was not changed by MK treatment. Furthermore, MK at 500 mg/kg·d reduced the tumor size and volume in AGS tumor xenografts. Taken together, MK may be useful for the prevention of cancer cell growth.

Gecko Proteins Exert Anti-Tumor Effect against Cervical Cancer Cells Via PI3-Kinase/Akt Pathway

  • Jeong, Ae-Jin;Chung, Chung-Nam;Kim, Hye-Jin;Bae, Kil-Soo;Choi, Song;Jun, Woo-Jin;Shim, Sang-In;Kang, Tae-Hong;Leem, Sun-Hee;Chung, Jin-Woong
    • The Korean Journal of Physiology and Pharmacology
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    • v.16 no.5
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    • pp.361-365
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    • 2012
  • Anti-tumor activity of the proteins from Gecko (GP) on cervical cancer cells, and its signaling mechanisms were assessed by viable cell counting, propidium iodide (PI) staining, and Western blot analysis. GP induced the cell death of HeLa cells in a dose-dependent manner while it did not affect the viability of normal cells. Western blot analysis showed that GP decreased the activation of Akt, and co-administration of GP and Akt inhibitors synergistically exerted anti-tumor activities on HeLa cells, suggesting the involvement of PI3-kinase/Akt pathway in GP-induced cell death of the cancer cells. Indeed, the cytotoxic effect of GP against HeLa cells was inhibited by overexpression of constituvely active form of Akt in HeLa cells. The candidates of the functional proteins in GP were analyzed by Mass-spectrum. Taken together, our results suggest that GP elicits anti-tumor activity against HeLa cells by inhibition of PI3-kinase/Akt pathway.

Isolation of a Quinone-rich Fraction from Ardisia crispa Roots and its Attenuating Effects on Murine Skin Tumorigenesis

  • Yeong, Looi Ting;Hamid, Roslida Abdul;Yazan, Latifah Saiful;Khaza'ai, Huzwah
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.4
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    • pp.2301-2305
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    • 2013
  • Ardisia crispa (Family: Myrsinaceae) is an evergreen, fruiting shrub that has been traditionally used as folklore medicine. Despite a scarcity of research publications, we have succeeded in showing suppressive effects on murine skin papillomagenesis. In extension, the present research was aimed at determining the effect of a quinone-rich fraction (QRF) isolated from the same root hexane extract on both initiation and promotion stages of carcinogenesis, at the selected dose of 30 mg/kg. Mice (groups I-IV) were initiated with a single dose of 7,12-dimethylbenz(${\alpha}$)anthracene (DMBA, $100{\mu}g/100{\mu}l$) followed by repeated promotion of croton oil (1%) twice weekly for 20 weeks. In addition, group I (anti-initiation) received QRF 7 days before and after DMBA; group II (anti-promotion) received QRF 30 minutes before each croton oil application; group III (anti-initiation/promotion) was treated with QRF as a combination of group I and II. A further two groups served as vehicle control (group V) and treated control (group VI). As carcinogen control, group IV showed the highest tumor volume ($8.79{\pm}5.44$) and tumor burden ($3.60{\pm}1.17$). Comparatively, group III revealed only 20% of tumor incidence, tumor burden ($3.00{\pm}1.00$) and tumor volume ($2.40{\pm}1.12$), which were significantly different from group IV. Group II also showed significant reduction of tumor volume (3.11), tumor burden (3.00) and tumor incidence (11.11%), along with prominent increase of latency period of tumor formation (week 12). Group I, nonetheless, demonstrated marked increment of tumor incidence by 40% with prompted latency period of tumor formation (week 7). No tumor formation was observed in groups V and VI. This study provided clear evidence of inhibitory effects of QRF during promotion period which was in agreement with our previous findings. The mechanism(s) underlying such effects have yet to be elucidated.

Anti-tumor Effects of Penfluridol through Dysregulation of Cholesterol Homeostasis

  • Wu, Lu;Liu, Yan-Yang;Li, Zhi-Xi;Zhao, Qian;Wang, Xia;Yu, Yang;Wang, Yu-Yi;Wang, Yi-Qin;Luo, Feng
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.1
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    • pp.489-494
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    • 2014
  • Background: Psychiatric patients appear to be at lower risk of cancer. Some antipsychotic drugs might have inhibitory effects on tumor growth, including penfluridol, a strong agent. To test this, we conducted a study to determine whether penfluridol exerts cytotoxic effects on tumor cells and, if so, to explore its anti-tumor mechanisms. Methods: Growth inhibition of mouse cancer cell lines by penfluridol was determined using the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Cytotoxic activity was determined by clonogenic cell survival and trypan blue assays. Animal tumor models of these cancer cells were established and to evaluate penfluridol for its anti-tumor efficacy in vivo. Unesterified cholesterol in cancer cells was examined by filipin staining. Serum total cholesterol and tumor total cholesterol were detected using the cholesterol oxidase/p-aminophenazone (CHOD-PAP) method. Results: Penfluridol inhibited the proliferation of B16 melanoma (B16/F10), LL/2 lung carcinoma (LL/2), CT26 colon carcinoma (CT26) and 4T1 breast cancer (4T1) cells in vitro. In vivo penfluridol was particularly effective at inhibiting LL/2 lung tumor growth, and obviously prolonged the survival time of mice bearing LL/2 lung tumors implanted subcutaneously. Accumulated unesterified cholesterol was found in all of the cancer cells treated with penfluridol, and this effect was most evident in LL/2, 4T1 and CT26 cells. No significant difference in serum cholesterol levels was found between the normal saline-treated mice and the penfluridol-treated mice. However, a dose-dependent decrease of total cholesterol in tumor tissues was observed in penfluridol-treated mice, which was most evident in B16/F10-, LL/2-, and 4T1-tumor-bearing mice. Conclusion: Our results suggested that penfluridol is not only cytotoxic to cancer cells in vitro but can also inhibit tumor growth in vivo. Dysregulation of cholesterol homeostasis by penfluridol may be involved in its anti-tumor mechanisms.

Interleukin-7 Enhances the in Vivo Anti-tumor Activity of Tumor-reactive CD8+ T cells with Induction of IFN-gamma in a Murine Breast Cancer Model

  • Yuan, Chun-Hui;Yang, Xue-Qin;Zhu, Cheng-Liang;Liu, Shao-Ping;Wang, Bi-Cheng;Wang, Fu-Bing
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.1
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    • pp.265-271
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    • 2014
  • Interleukin-7 (IL-7) is a potent anti-apoptotic cytokine that enhances immune effector cell functions and is essential for lymphocyte survival. While it known to induce differentiation and proliferation in some haematological malignancies, including certain types of leukaemias and lymphomas, little is known about its role in solid tumours, including breast cancer. In the current study, we investigated whether IL-7 could enhance the in vivo antitumor activity of tumor-reactive $CD8^+$ T cells with induction of IFN-${\gamma}$ in a murine breast cancer model. Human IL-7 cDNA was constructed into the eukaryotic expression plasmid pcDNA3.1, and then the recombinational pcDNA3.1-IL-7 was intratumorally injected in the TM40D BALB/C mouse graft model. Serum and intracellular IFN-${\gamma}$ levels were measured by ELISA and flow cytometry, respectively. $CD8^+$ T cell-mediated cytotoxicity was analyzed using the MTT method. Our results showed that IL-7 administration significantly inhibited tumor growth from day 15 after direct intratumoral injection of pcDNA3.1-IL-7. The anti-tumor effect correlated with a marked increase in the level of IFN-${\gamma}$ and breast cancer cells-specific CTL cytotoxicity. In vitro cytotoxicity assays showed that IL-7-treatment could augment cytolytic activity of $CD8^+$ T cells from tumor bearing mice, while anti-IFN-${\gamma}$ blocked the function of $CD8^+$ T cells, suggesting that IFN-${\gamma}$ mediated the cytolytic activity of $CD8^+$ T cells. Furthermore, in vivo neutralization of $CD8^+$ T lymphocytes by CD8 antibodies reversed the antitumor benefit of IL-7. Thus, we demonstrated that IL-7 exerts anti-tumor activity mainly through activating $CD8^+$ T cells and stimulating them to secrete IFN-${\gamma}$ in a murine breast tumor model. Based on these results, our study points to a potential novel way to treat breast cancer and may have important implications for clinical immunotherapy.

Study on Anti-tumor Activities of Both Hagocho and Byulap combined with Sambonggangyongbaneo-tang (삼봉강룡반어탕(三蓬薑龍半魚湯) 가(加) 하고초(夏枯草)와 加(가) 별갑(鱉甲)의 항암효과에 대한 비교연구)

  • Park, Jung-Sup;Jung, Seung-Min;Yim, Young-Nam;Ko, Ho-Yeun;Han, Ji-Wan;Kim, Dong-Woo
    • The Journal of Internal Korean Medicine
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    • v.25 no.4
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    • pp.242-251
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    • 2004
  • In this piece of research, Prunellae spica is added to Sambonggangyongbaneotang for one group and Trionycis carapax is added to Sambonggangyongbaneotang for the other group. With these two different prescriptions, the degrees of tumor suppression are compared to develop a better prescription. SKH = Sambonggangyongbaneo-tang + Prunellae Spica SKB = Sambonggangyongbaneo-tang + Trionycis Carapax The results were as follows: 1. SKH and SKB demonstrated anti-tumor effects against tumor advancement of S-180 2. SKH and SKB showed on elevation of macrophage for tumor-bearing mice. 3. $100{\mu}g/ml,\;500{\mu}g/ml$ of SKH and $500{\mu}g/ml$ of SKB demonstrated a rise in alkaline phosphates of B-Lymphocyte in the spleen in tumor-bearing mice. Results support a role for both SKH and SKB for anti-tumor effects via endorsement of macrophage and encouragement of B-lymphocyte toward S-180.

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