• Title/Summary/Keyword: Antitumor Activities

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Sanguinarine Induces Apoptosis in Human Hepatocellular Carcinoma HepG2 Cells through the Generation of ROS and Modulation of Akt/ERK Signaling Pathways (HepG2 인체 간암세포의 ROS 생성 및 ERK/Akt 신호전달 경로 조절을 통한 sanguinarine의 apoptosis 유도)

  • Hwang, Ju Yeong;Cho, Yung Hyun
    • Journal of Life Science
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    • v.25 no.9
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    • pp.984-992
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    • 2015
  • Sanguinarine is a benzophenanthridine alkaloid originally isolated from the roots of Sanguinaria canadensis. It has multiple biological activities (e.g., antioxidant and antiproliferative) and immune-enhancing potential. In this study, we explored the proapoptotic properties and modes of action of sanguinarine in human hepatocellular carcinoma HepG2 cells. Our results revealed that sanguinarine inhibited HepG2 cell growth and induced apoptosis in a dose-dependent manner. The induction of apoptosis by sanguinarine was associated with the up-regulation of Fas and Bax, the release of cytochrome c from the mitochondria to the cytosol, and the loss of the mitochondrial membrane potential. In addition, sanguinarine activated caspase-9 and -8, initiator caspases of the intrinsic and death extrinsic pathways, respectively, and caspase-3, accompanied by proteolytic degradation of poly (ADP-ribose) polymerase. Sanguinarine also triggered the generation of reactive oxygen species (ROS). The elimination of ROS by N-acetylcysteine reversed sanguinarine-induced apoptosis. Furthermore, sanguinarine induced the dephosphorylation of Akt and the phosphorylation of mitogen-activated protein kinases, including extracellular signal-regulated kinase (ERK), c-jun N-terminal kinase (JNK), and p38. The growth inhibition was enhanced by the combined treatment of sanguinarine with a phosphatidylinositol 3'-kinase (PI3K) inhibitor and an ERK inhibitor but not JNK and p38 inhibitors. Overall, our data indicate that the proapoptotic effects of sanguinarine in HepG2 cells depend on ROS production and the activation of both intrinsic and extrinsic signaling pathways, which is mediated by blocking PI3K/Akt and activating the ERK pathway. Thus, our data suggest that sanguinarine may be a natural compound with potential for use as an antitumor agent in liver cancer.

A Study on Antitumor Effect and Mechanism of Cortex ulmi pumilae Water Extract on HepG2 Hepatoma cell (유근피(楡根皮) 추출액(抽出液)이 HeoG2 간암세포(肝癌細胞)에 미치는 항암효과(抗癌效果) 및 기전(機轉)에 대(對)한 연구(硏究))

  • Choi, Su-Deock;Park, Young-Kweon;Kim, Gang-San;Kang, Byung-Ki;Han, Sang-Il
    • The Journal of Internal Korean Medicine
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    • v.21 no.2
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    • pp.259-266
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    • 2000
  • Objectives : The effects of aqueous extracts of Cortex ulmi pumilae (a traditional medicine for cancer treatment in oriental medicine) on the induction of apoptotic cell death were investigated in human liver origm hepatoma cell lines, HepG2. Methods : The death of HepG2 cells was markedly induced by the addition of extracts of Cortex ulmi pumilae in a dose-dependent manner. The apoptotic characteristic ladder pattern of DNA strand break was not observed in cell death of HepG2. In addition, it was not shown nucleus chromatin condensation and fragmentation under hoechst staining. However, by the using annexin V staining assay, externalizations of phosphatidylserine in HepG2 cell which were treated with Cortex ulmi pumilae extracts were detected in the early time (at 9 hr after extract treatment). Furthermore, LDH release was not detected in this early stage. Therefore, Cortex ulmi pumilae extracts-induced cell death of HepG2 cells is mediated by apoptotic death signal processes. Result : The activity of caspase 3-like proteases remained in a basal level in HepG2 cells which treated with the extract of Cordyceps sinensis. However, it was markedly increased in HepG2 cells which treated with two extracts of Cortex ulmi pumilae (C.U.P.-C, C.U.P.-K) which were differently extracted (respectively, 2.3 and 3.3 fold). On a while, the phosphotransferase activities of JNK1 was markedly induced in HepG2 cells which were treated with two extracts of Cortex ulmi pumilae. On the contrary, the activation of transcriptional activator, activating protein1(AP-1) and NF-kB were severely decreased by these two extracts of Cortex ulmi pumilae (C.U.P.-C, C.U.P.-K). In addition, antioxidants (GSH and NAC) and intracellular $Ca2^+$ level regulator (Bapta/AM and Thapsigargin) did not affect Cortex ulmi pumilae extracts-induced apoptotic death of HepG2 cells. Conclusions : In conclusion, our results suggest that two extracts of Cortex ulmi pumilae (C.U.P.-C, C.U.P.-K) induces the apoptotic death of human liver origin hepatoma HepG2 cells via activation of caspase 3-like proteases as well as JNK1, and inhibition of transcriptional activators, AP-1 and $NK-{\kappa}B$.

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Effects of Kimchi Extracts on the Growth of Sarcoma-180 Cells and Phagocytic Activity of Mice (김치추출물이 Sarcoma-180 세포의 성장과 마우스 식균활성에 미치는 효과)

  • Choi, Moung-Won;Kim, Kwang-Hyuk;Park, Kun-Young
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.26 no.2
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    • pp.254-260
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    • 1997
  • Effects of kimchi extracts on the immune response related to its antitumor activity in vitro and in vivo were investigated. The extracts of kimchi fermented for 0(fresh) and 3 weeks at $5^{\circ}C$ showed a direct cytotoxic effect on sarcoma-180 cells, tumor cells in vitro. Methanol extract(4mg/ml), MSF(methanol soluble fraction : 3mg/ml) and hexane extract(fresh : 2.0mg/ml, 3 weeks : 0.3mg/ml) of the kimchi(3 weeks, $5^{\circ}C$) markedly decreased the total numbers of sarcoma-180 cells, but not their viability. The phagocytic activity of peritoneal macrophage of mice was significantly augmented by these extracts of the kimchi compared with that of control in vitro and in vivo. These extracts also raised the phagocytic index, indicating that the number of phagocytized microbes per macrophage increased. Thus, kimchi might show a anti-tumor activity by enhancing the phagocytic cell activities.

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Cultivation of Cauliflower Mushroom (Sparassis crispa) Using Coniferous Sawdust-based Media with Barley Flours (보릿가루가 첨가된 침엽수 톱밥을 이용한 꽃송이버섯 재배)

  • Park, Hyun;Lee, Bong-Hun;Oh, Deuk-Sil;Ka, Kang-Hyeon;Bak, Won-Chull;Lee, Hak-Ju
    • Journal of Korea Foresty Energy
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    • v.24 no.2
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    • pp.31-36
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    • 2005
  • Cauliflower mushroom (Sparassis crispa) is an edible mushroom that shows remarkably high contents of $1,3-{\beta}-D-glucan$ compared to other edible mushrooms. The mushroom is known to give high antitumor and immunologic activities, thus the mushroom is recently cultivated in Japan and Korea. However, cultivation methods are being kept in secret or under patents by some companies with complicated procedures. This study was conducted to solve the problem by providing a simple method for the cultivation of cauliflower mushroom. We could produce the mushroom using sawdust-based media of Larix leptolepis, Pinus densiflora and P. koraiensis with addition of barley flours and sugar. The ratio of the sawdust : barley flours : sugar used for this study was 80:20:3 in dry-weight base, and the water content was adjusted as 65%. The productivity was somewhat different among the species of sawdust media and the strains of Sparassis crispa for the cultivation, and the mushroom production reached up to 177g from 650g base(productivity : 27%). Thus, this medium is strongly recommended as a practical cultivation method for cauliflower mushroom. By the way, further study for the determination of adequate concentration of barley flour and the selection of proper strain for each sawdust species is needed.

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Residual Nitrite Content and Storage Properties of Pork Patties Added with Gardenia Fructus Extract (치자 추출물이 돈육 패티의 아질산염 잔류량과 저장성에 미치는 영향)

  • Jeon, Mi-Ran;Choi, Seong-Hee
    • Food Science of Animal Resources
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    • v.31 no.5
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    • pp.741-747
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    • 2011
  • Gardenia fructus has been reported to have bioactivities of lowering blood glucose, antitumor, antithrombosis, repression of neogenesis of blood vessels, antioxidant and antibiosis. However, the nitrite scavenging activity and utilization in meat products have not been studied. The substitution effect for nitrite and antibiosis of Gardenia fructus extract (GFE) were investigated by measuring the residual nitrite contents and storage properties of pork patties prepared with nitrite (50, 100, and 150 ppm) and GFE (0, 0.25, 0.5%). The CIE $L^*$ and CIE $a^*$ of pork patties decreased, while CIE $b^*$ increased as the addition of GFE increased. Patties with more GFE added tended to be lower in pH when stored at $4^{\circ}C$ for 6 wk, but TBARS and VBN were not affected by the addition of GFE. Residual nitrite in patties was lowered as the storage period was lengthened and as the GFE addition was increased. During the storage at $4^{\circ}C$, Escherichia coli was not detected, and the total aerobic bacterial count was decreased as more GFE was added, showing the substitution effect of GFE for nitrite in antimicrobial activity. In conclusion, the results show that GFE has nitrite scavenging and antibiotic activities in meat products, suggesting its potential use in healthy and sustainable foods with diverse biofunctionalities.

Anti-proliferative Activities of Metallic Nanoparticles in an in Vitro Breast Cancer Model

  • Loutfy, Samah A;Al-Ansary, Nadia A;Abdel-Ghani, Nour T;Hamed, Ahmed R;Mohamed, Mona B;Craik, James D;Eldin, Taher A. Salah;Abdellah, Ahmed M;Hussein, Yassmein;Hasanin, MTM;Elbehairi, Serag Eldin I
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.14
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    • pp.6039-6046
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    • 2015
  • Aims: To investigate effect of metallic nanoparticles, silver (AgNPs) and gold nanoparticles (AuNPs) as antitumor treatment in vitro against human breast cancer cells (MCF-7) and their associated mechanisms. This could provide new class of engineered nanoparticles with desired physicochemical properties and may present newer approaches for therapeutic modalities to breast cancer in women. Materials and Methods: A human breast cancer cell line (MCF-7) was used as a model of cells. Metallic nanoparticles were characterized using UV-visible spectra and transmission electron microscopy (TEM). Cytotoxic effects of metallic nanoparticles on MCF-7 cells were followed by colorimetric SRB cell viability assays, microscopy, and cellular uptake. Nature of cell death was further investigated by DNA analysis and flow cytometry. Results: Treatment of MCF-7 with different concentrations of 5-10nm diameter of AgNPs inhibited cell viability in a dose-dependent manner, with IC50 value of $6.28{\mu}M$, whereas treatment of MCF-7 with different concentrations of 13-15nm diameter of AuNPs inhibited cell viability in a dose-dependent manner, with IC50 value of $14.48{\mu}M$. Treatment of cells with a IC50 concentration of AgNPs generated progressive accumulation of cells in the S phase of the cell cycle and prevented entry into the M phase. The treatment of cells with IC50 concentrations of AuNPs similarly generated progressive accumulation of cells in sub-G1 and S phase, and inhibited the entrance of cells into the M phase of the cell cycle. DNA fragmentation, as demonstrated by electrophoresis, indicated induction of apoptosis. Conclusions: Our engineered silver nanoparticles effectively inhibit the proliferation of human breast carcinoma cell line MCF-7 in vitro at high concentration ($1000{\mu}M$) through apoptotic mechanisms, and may be a beneficial agent against human carcinoma but further detailed study is still needed.

Antioxidant Properties of Various Microorganisms Isolated from Arctic Lichen Stereocaulon spp. (북극 지의류 Stereocaulon spp로부터 분리한 여러 미생물의 항산화 성질)

  • Kim, Mi-Kyeong;Park, Hyun;Oh, Tae-Jin
    • Microbiology and Biotechnology Letters
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    • v.41 no.3
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    • pp.350-357
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    • 2013
  • Lichens are symbiotic organisms composed of fungi, algae, or cyanobacteria which are able to survive in extreme environmental conditions ranging from deserts to polar areas. Some lichen symbionts produce a wide range of secondary metabolites that have many biological activities such as antibacterial, antifungal, antiviral, antitumor, antioxidant and anti-inflammatory etc. Among the symbionts of lichens, of the bacterial communities of lichen symbionts little is known. In this study, we isolated 4 microbial species from the Arctic lichen Stereocaulon spp. and evaluated their antioxidant properties using 1,1-diphenyl-2-picryl-hydrazyl assay as well as 2,2'-azino-bis(3-ethyl benzothiazoline-6-sulphonic acid) assay. Total phenolic contents and total flavonoid contents were also measured. A potent radical scavenging activity was detected in a number of the lichen extracts. Among the 4 species tested in this study, the ethyl acetate extract of Bosea vestrisii 36546(T) exhibited the strongest free radical scavenging activity, with an inhibition rate of 86.8% in DPPH and 75.2% in ABTS assays. Overall, these results suggest that lichen-bacteria could be a potential source of natural antioxidants.

Enhanced Production of Astaxanthin by Archaea Chaperonin in Escherichia coli (대장균에서 고세균 샤페론을 이용한 아스타잔틴 생산능 향상을 위한 연구)

  • Seo, Yong Bae;Lee, Jong Kyu;Jeong, Tae Hyug;Nam, Soo-Wan;Kim, Gun-Do
    • Journal of Life Science
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    • v.25 no.12
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    • pp.1339-1346
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    • 2015
  • The aim of this study is to increase production of carotenoids in recombinant Escherichia coli by Archaea chaperonin. The carotenoids are a widely distributed class of structurally and functionally diverse yellow, orange, and red natural pigments. These pigments are synthesized in bacteria, algae, fungi, and plants, and have been widely used as a feed supplement from poultry rearing to aquaculture. Carotenoids also exhibit diverse biological properties, such as strong antioxidant and antitumor activities, and enhancement of immune responses. In the microbial world, carotenoids are present in both anoxygenic and oxygenic photosynthetic bacteria and algae and in many fungi. We have previously reported cloning and functional analysis of the carotenoid biosynthesis genes from Paracoccus haeundaensis. The carotenogenic gene cluster involved in astaxanthin production contained seven carotenogenic genes (crtE, crtB, crtI, crtY, crtZ, crtW and crtX genes) and recombinant Escherichia coli harboring seven carotenogenic genes from Paracoccus haeundaensis produced 400 μg/g dry cell weight (DCW) of astaxanthin. In order to increase production of astaxanthin, we have co-expressed chaperone genes (ApCpnA and ApCpnB) in recombinant Escherichia coli harboring the astaxanthin biosynthesis genes. This engineered Escherichia coli strain containing both chaperone gene and astaxanthin biosynthesis gene cluster produced 890 μg/g DCW of astaxanthin, resulting 2-fold increased production of astaxanthin.

Isolation of Anticarcinogenic Isoflavone-conjugated Glycoproteins from a Submerged Liquid Culture of Agaricus blazei Mycelia by the Autolysis Process (신령버섯균사체 액체배양물의 자가분해에 의한 항암성 isoflavone-conjugated glycoprotein 분리)

  • Kim, So Young;Kim, Young Suk;Jang, Joung Soon;Kim, Boh Hyun;Rakib, Abdur Md.;Kim, Gon Sup;Kim, Jeong Ok;Ha, Yeong Lae
    • Journal of Life Science
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    • v.24 no.12
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    • pp.1316-1324
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    • 2014
  • Most beta-glucans obtained from various fruit bodies of mushrooms and mushroom mycelial cultures have high-molecular weight glycoproteins, conjugated with beta-glucans. We report that isoflavone-conjugated glycolproteins (designated as gluvone) were isolated and exhibited stronger anticarcinogenic activities. Agaricus blazei mycelia (ABM) was cultured in a liquid medium containing soybean flakes for 14 days. The liquid culture was autolyzed by incubating at $53^{\circ}C$ (pH 5.5) for 3 h. A crude glycoprotein (CGP) fraction with a cytotoxic effect on a mouse ascite cancer cell line (S-180) and a human breast cancer cell line (MCF-7) was isolated from the autolyzed ABM cultures by 80% ethanol treatment. Gluvone was isolated from the CGP with Sephadex G-75 column chromatography. It exhibited a stronger anticancer effect than CGP against the S-180 cell-induced female ICR mouse ascites carcinogenesis. Gluvone with 9,400 daltons was identified as a glycoprotein conjugated with isoflavone. According to HPLC and GC analysis, in conjunction with $^1H$-NMR spectral analysis, it contained 60% carbohydrates (glucose, fructose, and ribose), 31% protein, and 2% isoflavone (daidzein and genistein), which is a novel material. These results indicate that a strong anticarcinogenic gluvone was isolated from the autolyzed product of a submerged liquid culture of ABM, suggesting that autolysis could be a useful tool to produce antitumor agents.

Optimal Conditions of Mycelial Growth and Exopolysaccharide Production in Submerged Culture of Phellinus baumii (Phellinus baumii으로부터 세포외 다당체 생산의 최적화)

  • Hwang, Hye-Jin;Kim, Sang-Woo;Yun, Jong-Won;Park, Jang-Won
    • Journal of Life Science
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    • v.14 no.1
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    • pp.51-56
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    • 2004
  • The polysaccharide isolated from Phellinus species has been known as a folk remedy, including antitumor and immune-stimulating activities. However, there are lacks of knowledge about mycelial growth and exopolysaccharide (EH) production in its submerged culture. We investigated the optimal conditions on mycelial growth and EPS production in Phellinus baumii. The optimal temperature and initial pH for mycelial growth and EPS production in shake flask culture of P. baumii were proved to be 3$0^{\circ}C$ and pH 5.0, respectively. In case of carbon source, cellobiose and maltose were highly efficient for mycelial growth and fructose and mannitol were also relatively favorable for EPS production. Yeast extract was the most suitable nitrogen source for mycelial growth and EPS production. The composition of optimal culture medium was determined to be fructose 20 g/L, yeast extract 20 g/L, and $CaCl_2$ 0.55 g/L, respectively. Under the optimal culture condition, the maximum mycelial biomass and EPS achieved in a 5-L stirred-tank fermenter were 17.43 g/L and 3.6 g/L, respectively. It was found that the EPS was a glycoprotein onsisted of mainly arginine (14.1%) and glycine (12.0 %) in protein moiety and mainly mannose (48.7%) and arabinose (38.4%) in carbohydrate moiety.