• Title/Summary/Keyword: Cytotoxic Effect

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Siamese Crocodile White Blood Cell Extract Inhibits Cell Proliferation and Promotes Autophagy in Multiple Cancer Cell Lines

  • Phosri, Santi;Jangpromma, Nisachon;Chang, Leng Chee;Tan, Ghee T.;Wongwiwatthananukit, Supakit;Maijaroen, Surachai;Anwised, Preeyanan;Payoungkiattikun, Wisarut;Klaynongsruang, Sompong
    • Journal of Microbiology and Biotechnology
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    • v.28 no.6
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    • pp.1007-1021
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    • 2018
  • Cancer represents one of the most significant threats to human health on a global scale. Hence, the development of effective cancer prevention strategies, as well as the discovery of novel therapeutic agents against cancer, is urgently required. In light of this challenge, this research aimed to evaluate the effects of several potent bioactive peptides and proteins contained in crocodile white blood cell extract (cWBC) against LU-1, LNCaP, PC-3, MCF-7, and CaCo-2 cancer cell lines. The results demonstrate that 25, 50, 100, and $200{\mu}g/ml$ cWBC exhibits a strong cytotoxic effect against all investigated cell lines ($IC_{50}$ $70.34-101.0{\mu}g/ml$), while showing no signs of cytotoxicity towards noncancerous Vero and HaCaT cells. Specifically, cWBC treatment caused a significant reduction in the cancerous cells' colony forming ability. A remarkable suppression of cancerous cell migration was observed after treatment with cWBC, indicating potent antimetastatic properties. The mechanism involved in the cancer cell cytotoxicity of cWBC may be related to apoptosis induction, as evidenced by typical apoptotic morphology features. Moreover, certain cWBC concentrations induced significant overproduction of ROS and significantly inhibited the $S-G_2/M$ transition in the cancer cell. The molecular mechanisms of cWBC in apoptosis induction were to decrease Bcl-2 and XIAP expression levels and increase the expression levels of caspase-3, caspase-8, and p53. These led to a decrease in the expression level of the cell cycle-associated gene cyclin-B1 and the arrest of cell population growth. Consequently, these findings demonstrate the prospect of the use of cWBC for cancer therapy.

Quantification of 4-Hydroxyalkenals in Oils Consumed in Korea (상용하는 식물성 기름에서 지질과산화의 독성물질 4-hydroxy-2-alkenals 정량)

  • Surh, Jeong-Hee;Kwon, Hoon-Jeong
    • Korean Journal of Food Science and Technology
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    • v.34 no.5
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    • pp.905-910
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    • 2002
  • 4-Hydroxyalkenals are cytotoxic aldehydes generated by the oxidation of n-6 and n-3 polyunsaturated fatty acids. To evaluate the potential risk of 4-hydroxyalkenals on Koreans, quantitative data of various oils are necessary. Simultaneous monitoring of 4-hydroxyhexenal and 4-hydroxynoneal in 39 samples including new and used ones through single ion monitoring mode of GC/MS detected both aldehydes in all samples tested, ranging from 0.21 to 26.9 nmol/g for 4-hydroxy-2-hexenal and 0.06 to 56.6 nmol/g for 4-hydroxy-2-nonenal. Frying oils collected from local markets showed 2.28-7.90 and 8.31-30.5 nmol/g of 4-hydroxyhexenal and 4-hydroxynoneal, respectively. National health and nutrition survey data were employed to determine the exposure effect to these 4-hydroxyalkenals from the four most consumed oils in Korea. Daily exposures to hydroxyalkenals excluding possible exposure from fried food were $1.9\;{\mu}g$ from soybean oil, $0.5\;{\mu}g$ from sesame oil, $0.2\;{\mu}g$ from corn oil, and $0.1\;{\mu}g$ from perilla oil. Due to the increasing consumption of polyunsaturated fatty acids in Korea, these data may provide valuable information for evaluating possible physiological effects of 4-hydroxyalkenals from vegetable oils.

Antiviral activity of ginsenosides against coxsackievirus B3, enterovirus 71, and human rhinovirus 3

  • Song, Jae-Hyoung;Choi, Hwa-Jung;Song, Hyuk-Hwan;Hong, Eun-Hye;Lee, Bo-Ra;Oh, Sei-Ryang;Choi, Kwangman;Yeo, Sang-Gu;Lee, Yong-Pyo;Cho, Sungchan;Ko, Hyun-Jeong
    • Journal of Ginseng Research
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    • v.38 no.3
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    • pp.173-179
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    • 2014
  • Background: Ginsenosides are the major components responsible for the biochemical and pharmacological actions of ginseng, and have been shown to have various biological activities. In this study, we investigated the antiviral activities of seven ginsenosides [protopanaxatriol (PT) type: Re, Rf, and Rg2; protopanaxadiol (PD) type: Rb1, Rb2, Rc, and Rd)] against coxsackievirus B3 (CVB3), enterovirus 71 (EV71), and human rhinovirus 3 (HRV3). Methods: Assays of antiviral activity and cytotoxicity were evaluated by the sulforhodamine B method using the cytopathic effect (CPE) reduction assay. Results: The antiviral assays demonstrated that, of the seven ginsenosides, the PT-type ginsenosides (Re, Rf, and Rg2) possess significant antiviral activities against CVB3 and HRV3 at a concentration of $100{\mu}g/mL$. Among the PT-type ginsenosides, only ginsenoside Rg2 showed significant anti-EV71 activity with no cytotoxicity to cells at $100{\mu}g/mL$. The PD-type ginsenosides (Rb1, Rb2, Rc, and Rd), by contrast, did not show any significant antiviral activity against CVB3, EV71, and HRV3, and exhibited cytotoxic effects to virus-infected cells. Notably, the antiviral efficacies of PT-type ginsenosides were comparable to those of ribavirin, a commonly used antiviral drug. Conclusion: Collectively, our findings suggest that the ginsenosides Re, Rf, and Rg2 have the potential to be effective in the treatment of CVB3, EV71, and HRV3 infection.

Deoxypodophyllotoxin Induces a Th1 Response and Enhances the Antitumor Efficacy of a Dendritic Cell-based Vaccine

  • Lee, Jun-Sik;Kim, Dae-Hyun;Lee, Chang-Min;Ha, Tae-Kwun;Noh, Kyung-Tae;Park, Jin-Wook;Heo, Deok-Rim;Son, Kwang-Hee;Jung, In-Duk;Lee, Eun-Kyung;Shin, Yong-Kyoo;Ahn, Soon-Cheol;Park, Yeong-Min
    • IMMUNE NETWORK
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    • v.11 no.1
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    • pp.79-94
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    • 2011
  • Background: Dendritic cell (DC)-based vaccines are currently being evaluated as a novel strategy for tumor vaccination and immunotherapy. However, inducing long-term regression in established tumor-implanted mice is difficult. Here, we show that deoxypohophyllotoxin (DPT) induces maturation and activation of bone marrow-derived DCs via Toll-like receptor (TLR) 4 activation of MAPK and NF-${\kappa}B$. Methods: The phenotypic and functional maturation of DPT-treated DCs was assessed by flow cytometric analysis and cytokine production, respectively. DPT-treated DCs was also used for mixed leukocyte reaction to evaluate T cell-priming capacity and for tumor regression against melanoma. Results: DPT promoted the activation of $CD8^+$ T cells and the Th1 immune response by inducing IL-12 production in DCs. In a B16F10 melanoma-implanted mouse model, we demonstrated that DPT-treated DCs (DPT-DCs) enhance immune priming and regression of an established tumor in vivo. Furthermore, migration of DPT-DCs to the draining lymph nodes was induced via CCR7 upregulation. Mice that received DPT-DCs displayed enhanced antitumor therapeutic efficacy, which was associated with increased IFN-${\gamma}$ production and induction of cytotoxic T lymphocyte activity. Conclusion: These findings strongly suggest that the adjuvant effect of DPT in DC vaccination is associated with the polarization of T effector cells toward a Th1 phenotype and provides a potential therapeutic antitumor immunity.

Biological Activities of Ethanol Extract from Corni fructus (산수유 에탄올 추출물의 생리활성)

  • Kwon, Seong-Hyuk;Yang, Hee-Sun;Kim, Jae-Yong;Park, Kyoung-Wuk;Shon, Mi-Yae;Kang, Kap-Suk;Shim, Ki-Hwan;Seo, Kwon-Il
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.38 no.3
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    • pp.287-291
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    • 2009
  • In order to use Corni fructus as functional food materials, we investigated the biological activities of ethanol extracts from Corni fructus (EECF). The hydrogen-donating activity of EECF was increased in a dose dependent manner compared with untreated control, and the activities by EECF were 64 and 74% at 300 and $500{\mu}g/mL$ concentration, respectively. The NO productions in the RAW264.7 marcrophage cells treated with EECF were increased in dose dependent manners. EECF significantly inhibited the growth of MCF-7 human breast cancer cells in dose and time dependent manners. EECF of $500{\mu}g/mL$ concentration inhibited the proliferation by over 60% in the MCF-7 cells when treated for 72 hr. Also, the proliferations were increased in the MCF-7 cells cultured in the charcoal-treated FBS (cFBS) medium with environmental hormones such as bisphenol or $17{\beta}$-estradiol of $0.1{\mu}M$ whereas the proliferations were decreased in the MCF-7 cells treated with the environmental hormones after treatment of EEFC for 72 hr. The results suggest that Corni fructus would be used as functional food materials.

Inhibition of Differentiation and Anti-Adipogenetic Effect of the Salvia plebeia R. Br. Ethanol Extract in Murine Adipocytes, 3T3-L1 Cells (배암차즈기 에탄올 추출물의 3T3-L1 지방전구세포 분화 억제 및 지방 축적 저해 효과)

  • Kim, Sung-Ok;Kim, Mi-Ryeo;Hwang, Kyung-A;Park, No-Jin;Jeong, Ji-Suk
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.46 no.4
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    • pp.401-408
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    • 2017
  • Salvia plebeia R. Br. (Lamiaceae) has been used in folk medicines in Asian countries, including Korea and China, to treat inflammatory diseases. The focus of our research was on the anti-adipogenic activity of ethanol extract from Salvia plebeia R. Br. (SPE) in 3T3-L1 adipocytes. This study investigated inhibition of differentiation and lipogenesis upon SPE treatment in 3T3-L1 cells. The results reveal that SPE at non-cytotoxic concentration significantly suppressed triglyceride accumulation and reduced expression of peroxisome proliferator-activated receptor gamma, CCAAT/enhancer-binding protein-alpha, and sterol regulatory element-binding protein as adipogenic transcription factors in 3T3-L1 adipocytes compared to non-treated control cells. Inducible phosphorylation of AMP-activated protein kinase, acetyl CoA carboxylase, and hormone-sensitive lipase as well as carnitine palmitoyltransferase-1 mRNA expression increased upon SPE treatment, which suppressed expression of fatty acid synthase. In conclusion, these results demonstrate that SPE can inhibit expression of adipogenic genes in 3T3-L1 adipocytes. Our study suggests that SPE has potential anti-obesity effects and is a novel therapeutic functional agent with anti-adipogenic activity via reduction of lipogenesis.

Effect of Growth Inhibition and Quinone Reductase Activity Stimulation of Makgeoly Fractions in Various Cancer Cells (막걸리 분획물에 의한 암세포 성장 억제 및 Quinone Reductase 활성 증가 효과)

  • Shin, Mi-Ok;Kang, Dae-Yeon;Kim, Mi-Hyang;Bae, Song-Ja
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.37 no.3
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    • pp.288-293
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    • 2008
  • In this study, we investigated the anticancer activity of Makgeoly (MG). MG was fractionated into four fractions by using solvent partition method, affording hexane (MGH), methanol (MGM), butanol (MGB) and aquous (MGA) soluble fractions. We determined the cytotoxicity of these four fractions in four kinds of cancer cell lines, such as HepG2, MCF-7, B16-F10 and HT29 by MTT assay. Among the various fractions, the MGM showed the strongest cytotoxic effects on all cancer cell lines. The morphological changes such as membrane shrinking and blebbing of cells were also observed by MGM treatment in HepG2 cell. In addition, we observed quinone reductase (QR) activity stimulating effects in all fraction layers of MG on HepG2 cells. QR activity increased approximately 2.6 and 2.1 times in MGM and MGH treated HepG2 cell at $100{\mu}g/mL$, respectively, compared to that in control value. Although further studies are needed, the present work could suggest that the fin of MG has a potential to be used as a chemopreventive agent against cancer.

Antioxidative and Biological Activities of Santalum album Extracts by Extracting Methods (추출방법에 따른 백단향의 항산화 및 생리활성)

  • Kim, Tae-Hoon
    • Food Science and Preservation
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    • v.15 no.3
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    • pp.456-460
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    • 2008
  • Santalum album has been used as a folk medicine for treatment of skin diseases, inflammation, gonorrhea, gleet, and cystitis in India and other Asian countries. In a search for possible bioactive agents from natural sources, we found that the various solvent extracts of S. album showed significant antioxidative effect in 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity test and moderate other biological functions submitted to the several bioassay systems for whitening and cytotoxicity evaluations. Among the tested extracts displayed DPPH radical scavenging activity, and the 70% acetone extract showed the most potent activity with an $IC_{50}$ value of $18.6\;{\mu}g/ml$, more potent than a positive control, L-ascorbic acid ($IC_{50}$, $28.7\;{\mu}g/mL$). Also, anti-lipid peroxidation, tyrosinase inhibitory, and cytotoxic effects were determined in each experiment. Total phenolic content of 70% acetone extract was found to be 117.1 mg equivalent of gallic acid per g of extract. Previous phytochemical investigation reveals the presence of phenolic compounds. The results indicate that S. album possess potential antioxidant activity and phenolic constituents are responsible for this capacity.

The Effects of BGG on Various Immunological Factors Related to Pathogenesis of Allergic Dermatitis in NC/Nga Mice Induced by Der-f (보음거풍지양탕(補陰祛風止痒湯)이 아토피 피부염을 유발(誘發)한 NC/Nga 생쥐의 면역(免疫) 조절작용(調節作用)에 미치는 영향(影響))

  • Bang, Chan-Kuk;Choi, Jeong-Jun;Eom, Dong-Myung;Kim, Dong-Hee
    • Journal of Haehwa Medicine
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    • v.16 no.2
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    • pp.147-169
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    • 2007
  • To evaluate the therapeutic effects of BGG on atopic dermatitis, we investigated the composition of immune cells of lymph node, PBMC and skin of Dermatophagoides farinae-induced NC/Nga mice. The levels of immunoglobulins in serum were analyzed at the protein level and the amount of pathologic cytokines were investigated using CD3/CD28 stimulated splenocytes. The results are summarized below; 1. BGG showed no cytotoxic effect up to $200\;{\mu}g/m{\ell}$ on mLFC in vitro. 2. BGG showed no hepatotoxicity in vivo based on the levels of ALT and AST. 3. Atopic dermatitis was improved through naked eye examination. BGG reduced the skin clinical index from 2.9 to 1.3 (p<0.01). 4. H&E and toluidine blue staining of tissue biopsies revealed that BGG inhibited the infiltration of lymphocytes and mast cells to skin. 5. BGG reduced the number of CD19 positive B cells in PBMCs by 16% (p<0.01), whereas cells were increased by 26% (p<0.05) in lymph nodes. 6. BGG reduced the numbers of B220+/CD23+ cells by 15% (p<0.01) and 33% in PBMCs and lymph node, respectively. 7. BGG reduced the numbers of B220+/IgE+ cells in PBMCs and lymph node by 21% and 33% (p<0.01), respectively. 8. BGG suppressed the levels of IgE (13%, p<0.001) as well as IgM (34%, p<0.001), IgG2a (40%, p<0.001) and IgG2b (26%, p<0.05). 9. BGG reduced the levels of IL-4 and IFN-$\gamma$ by 7% (p<0.05) and 13% (p<0.001) in anti-CD3 and anti-CD28-activated splenocytes, respectively. 10. BGG considerably inhibited the production of TNF-$\alpha$ and IL-6 by 42% (p<0.01) and 15% in the serum, respectively. Based on the results above, we concluded that BGG has therapeutic effects on atopic dermatitis by regulating the differentiation of B cells and isotype switching of IgE. Further investigations on the molecular mechanisms of BGG on atopic dermatitis are anticipated.

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Removal of ZnO Nanoparticles in Aqueous Phase and Its Ecotoxicity Reduction (수계 내 ZnO 나노입자의 제거 및 생태독성 저감)

  • Kim, Hyunsang;Kim, Younghun;Kim, Younghee;Lee, Sangku
    • Clean Technology
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    • v.22 no.2
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    • pp.89-95
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    • 2016
  • The nanotoxicity of ZnO nanoparticles used in cosmetics and tire industry is one of emerged issues. Herein, the removal of ZnO nanoparticles dispersed in aqueous phase and its ecotoxicity were investigated. In the short-term exposure for fertilized eggs (O. latipes), the deformity was observed at 5 mg L−1 of ZnO nanoparticles in some individuals and delayed hatching of eggs by retarded growth was observed at 10 mg L−1 of ZnO nanoparticles. This result show that ZnO nanoparticles have cytotoxic effect to the organisms lived in water phase. Therefore, herein, the removal of ZnO nanoparticles in aqueous phase by chemical precipitation was investigated. After addition of Na2S and Na2HPO4, the precipitated ZnO was transformed to ZnS and Zn3(PO4)2 particles, respectively. The removal efficiency of ZnO was reached to almost 100% for two cases. In addition, the toxicity tests about ZnS and Zn3(PO4)2 particles showed no acute toxicity for D. magna. This implies that transformation of ZnO to ZnS and Zn3(PO4)2 particles with very low ionization constant might decrease effectively the toxicity of ZnO.