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1.
The present study investigated possible mechanisms on the apoptosis induction of human leukemic cells by fucoidan, a sulfated polysaccharide found in marine algae. Fucoidan treatment of cells resulted in inhibition of growth and induction of apoptosis, as measured by 3-(4,5-dimetylthiazol-2-yl)-2,5-diphenyl-tetrazolium (MTT) assay, fluorescence microscopy, DNA fragmentation, and flow cytometry analysis. The increase in apoptosis was associated with the proteolytic activation of caspases, Bid cleavage, insertion of pro-apoptotic Bax into the mitochondria, release of cytochrome c from mitochondria to cytosol, and loss of mitochondria membrane potential (MMP) in U937 cells. However, apoptosis induced by fucoidan was attenuated by caspase inhibitors, indicating that fucoidan-induced apoptosis was dependent on the activation of caspases. Furthermore, fucoidan treatment effectively activated the p38 mitogen-activated protein kinase (MAPK) and p38 MAPK inhibitor, SB203580, and significantly reduced fucoidan-induced apoptosis through inhibition of Bax translocation and caspases activation, suggesting that the activation of p38 MAPK may play a key role in fucoidan-induced apoptosis. In addition, the authors found fucoidan-induced significantly attenuated in Bcl-2 overexpressing U937 cells, and pretreatment with fucoidan and HA 14-1, a small-molecule Bcl-2 inhibitor, markedly increased fucoidan-mediated apoptosis in Bcl-2 overexpressing U937 cells. Our findings imply that we may attribute some of the biological functions of p38 MAPK and Bcl-2 to their ability to inhibit fucoidan-induced apoptosis.  相似文献   

2.
Fucoidan, a sulfated polysaccharide, has a variety of biological activities, such as anti-cancer, anti-angiogenic and anti-inflammatory. However, the mechanisms of action of fucoidan as an anti-cancer agent have not been fully elucidated. The present study examined the anti-cancer effect of fucoidan obtained from Undaria pinnatifida in PC-3 cells, human prostate cancer cells. Fucoidan induced the apoptosis of PC-3 cells by activating both intrinsic and extrinsic pathways. The induction of apoptosis was accompanied by the activation of extracellular signal-regulated kinase mitogen-activated protein kinase (ERK1/2 MAPK) and the inactivation of p38 MAPK and phosphatidylinositol 3-kinase (PI3K)/Akt. In addition, fucoidan also induced the up-regulation of p21Cip1/Waf and down-regulation of E2F-1 cell-cycle-related proteins. Furthermore, in the Wnt/β-catenin pathway, fucoidan activated GSK-3β that resulted in the decrease of β-catenin level, followed by the decrease of c-myc and cyclin D1 expressions, target genes of β-catenin in PC-3 cells. These results suggested that fucoidan treatment could induce intrinsic and extrinsic apoptosis pathways via the activation of ERK1/2 MAPK, the inactivation of p38 MAPK and PI3K/Akt signaling pathway, and the down-regulation of Wnt/β-catenin signaling pathway in PC-3 prostate cancer cells. These data support that fucoidan might have potential for the treatment of prostate cancer.  相似文献   

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Fucose-containing sulfated polysaccharides (FCSPs) extracted from seaweeds, especially brown macro-algae, are known to possess essential bioactive properties, notably growth inhibitory effects on tumor cells. In this work, we conducted a series of in vitro studies to examine the influence of FCSPs products from Sargassumhenslowianum C. Agardh (FSAR) and Fucus vesiculosus (FVES), respectively, on proliferation of melanoma B16 cells and to investigate the underlying apoptosis promoting mechanisms. Cell viability analysis showed that both FCSPs products, i.e., FSAR and FVES, decreased the proliferation of the melanoma cells in a dose-response fashion, with FSAR being more potent at lower dosages, and FVES being relatively more anti-proliferative than FSAR at higher dosages. Flow cytometric analysis by Annexin V staining of the melanoma cells exposed to the FCSPs products confirmed that both FSAR and FVES induced apoptosis. The FCSPs-induced apoptosis was evidenced by loss of plasma membrane asymmetry and translocation of the cell membrane phospholipids and was accompanied by the activation of caspase-3. The FCSPs bioactivity is proposed to be attributable to distinct structural features of the FCSPs, particularly the presence of sulfated galactofucans (notably in S.henslowianum) and sulfated fucans (notably in F. vesiculosus). This study thus indicates that unfractionated FCSPs may exert bioactive effects on skin cancer cells via induction of apoptosis through cascades of reactions that involve activation of caspase-3.  相似文献   

6.
Excessive alcohol consumption can lead to brain tissue damage and cognitive dysfunction. Acetaldehyde, the most toxic metabolite of ethanol, mediates the brain tissue damage and cognitive dysfunction induced by chronic excessive alcohol consumption. In this study, the effect of astaxanthin, a marine bioactive compound, on acetaldehyde-induced cytotoxicity was investigated in SH-SY5Y cells. It was found that astaxanthin protected cells from apoptosis by ameliorating the effect of acetaldehyde on the expression of Bcl-2 family proteins, preventing the reduction of anti-apoptotic protein Bcl-2 and the increase of pro-apoptotic protein Bak induced by acetaldehyde. Further analyses showed that astaxanthin treatment inhibited acetaldehyde-induced reduction of the levels of activated Akt and cyclic AMP-responsive element binding protein (CREB). Astaxanthin treatment also prevented acetaldehyde-induced increase of the level of activated p38 mitogen-activated protein kinase (MAPK) and decrease of the level of activated extracellular signal-regulated kinases (ERKs). Activation of Akt/CREB pathway promotes cell survival and is involved in the upregulation of Bcl-2 gene. P38MAPK plays a critical role in apoptotic events while ERKs mediates the inhibition of apoptosis. Thus, astaxanthin may inhibit acetaldehyde-induced apoptosis through promoting the activation of Akt/CREB and ERKs and blocking the activation of p38MAPK. In addition, astaxanthin treatment suppressed the oxidative stress induced by acetaldehyde and restored the antioxidative capacity of SH-SY5Y cells. Therefore, astaxanthin may protect cells against acetaldehyde-induced cytotoxicity through maintaining redox balance and modulating apoptotic and survival signals. The results suggest that astaxanthin treatment may be beneficial for preventing neurotoxicity associated with acetaldehyde and excessive alcohol consumption.  相似文献   

7.
The influence of flaxseed (Linum usitatissimum L.) and its total non-digestible fraction (TNDF) on the expression of genes involved in azoxymethane (AOM)-induced colon cancer in Sprague Dawley rats was analyzed. The dose used in the animal model was two tablespoons of flaxseed per day, which is the dose recommended for humans. Flaxseed significantly decreased the crypt multiplicity (10.50?±?3.5) compared with the AOM treatment (34.00?±?11.0), which suggests that flaxseed exhibits a preventive effect against colon cancer. Both treatments (flaxseed and TNDF) influence the overexpression of genes involved in cell cycle arrest and mitochondrial apoptosis: p53, p21, bcl-2, bax and caspase-3. Flaxseed induced the expression of p53 and p21, whereas TNDF triggered the p21-independent expression of p53. This finding suggests that both of these treatments induced cell cycle arrest. In addition, TNDF induced mitochondrial apoptosis because the TNDF + AOM group exhibited the expression of caspase-3, decreased bcl-2 expression and increased bax expression. These results suggest that the expression of the analyzed genes is associated with the presence of dietary antioxidants linked to the cell wall of flaxseed.  相似文献   

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10.
Fucoidans, fucose-enriched sulfated polysaccharides isolated from brown algae and marine invertebrates, have been shown to exert anticancer activity in several types of human cancer, including leukemia and breast cancer and in lung adenocarcinoma cells. In the present study, the anticancer activity of the fucoidan extracted from the brown seaweed Undaria pinnatifida was investigated in human hepatocellular carcinoma SMMC-7721 cells, and the underlying mechanisms of action were investigated. SMMC-7721 cells exposed to fucoidan displayed growth inhibition and several typical features of apoptotic cells, such as chromatin condensation and marginalization, a decrease in the number of mitochondria, and in mitochondrial swelling and vacuolation. Fucoidan-induced cell death was associated with depletion of reduced glutathione (GSH), accumulation of high intracellular levels of reactive oxygen species (ROS), and accompanied by damage to the mitochondrial ultrastructure, depolarization of the mitochondrial membrane potential (MMP, Δψm) and caspase activation. Moreover, fucoidan led to altered expression of factors related to apoptosis, including downregulating Livin and XIAP mRNA, which are members of the inhibitor of apoptotic protein (IAP) family, and increased the Bax-to-Bcl-2 ratio. These findings suggest that fucoidan isolated from U. pinnatifida induced apoptosis in SMMC-7721 cells via the ROS-mediated mitochondrial pathway.  相似文献   

11.
Fucan is a term that defines a family of homo- and hetero-polysaccharides containing sulfated l-fucose in its structure. In this work, a heterofucan (F2.0v) from the seaweed, Dictyota menstrualis, was evaluated as an antinociceptive and anti-inflammatory agent. F2.0v (20.0 mg/kg) inhibits 100% of leukocyte migration into the peritoneal cavity after chemical stimulation. However, F2.0v does not alter the expression of interleukin-1 beta (IL-1β) and interleukin-6 (IL-6), as well as tumor necrosis factor alpha (TNF-α). F2.0v (20.0 mg/kg) has peripheral antinociceptive activity with potency similar to dipyrone. On the other hand, it had no effect on pain response on the hot plate test. Confocal microscopy analysis and flow cytometry showed that F2.0v binds to the surface of leucocytes, which leads us to suggest that the mechanism of action of anti-inflammatory and antinociceptive F2.0v is related to its ability to inhibit the migration of leukocytes to the site of tissue injury. In summary, the data show that F2.0v compound has great potential as an antinociceptive and anti-inflammatory, and future studies will be performed to further characterize the mechanism of action of F2.0v.  相似文献   

12.
Fucan is a term used to denominate a type of polysaccharide which contains substantial percentages of l-fucose and sulfate ester groups. We obtained five heterofucans from Sargassum filipendula by proteolytic digestion followed by sequential acetone precipitation. These heterofucans are composed mainly of fucose, glucose, glucuronic acid, galactose and sulfate. These fucans did not show anticoagulant activity in PT and aPTT tests. Their antioxidant activity was evaluated using the follow tests; total antioxidant capacity, scavenging hydroxyl and superoxide radicals, reducing power and ferrous ion [Fe(II)] chelating. All heterofucans displayed considerable activity, especially SF-1.0v which showed the most significant antioxidant potential with 90.7 ascorbic acid equivalents in a total antioxidant capacity test and similar activity when compared with vitamin C in a reducing power assay. The fucan antiproliferative activity was performed with HeLa, PC3 and HepG2 cells using MTT test. In all tested conditions the heterofucans exhibited a dose-dependent effect. The strongest inhibition was observed in HeLa cells, where SF-1.0 and SF-1.5 exhibited considerable activity with an IC50 value of 15.69 and 13.83 μM, respectively. These results clearly indicate the beneficial effect of S. filipendula polysaccharides as antiproliferative and antioxidant. Further purification steps and additional studies on structural features as well as in vivo experiments are needed to test the viability of their use as therapeutic agents.  相似文献   

13.
Sepia ink oligopeptide (SIO) is a tripeptide extracted from Sepia ink. To test the hypothesis that SIO inhibits prostate cancer by inducing apoptosis, the effects of SIO on the proliferation of three human prostate cancer cell lines were examined using a CCK-8 assay. SIO significantly inhibited the proliferation of DU-145, PC-3 and LNCaP cells in a time- and dose-dependent manner. Flow cytometry studies showed that exposing DU-145, PC-3 and LNCaP cells to 5, 10, or 15 mg/mL SIO for 24 h increased the percentage of the early-stage apoptotic cells from 11.84% to 38.26% (DU-145), 22.76% to 39.96% (PC-3) and 5.05% to 16.11% (LNCaP), respectively. In addition, typical morphologic changes were observed in the cells with acridine orange/ethidium bromide staining. SIO treatment induced strong S and G2/M phase cell cycle arrest in a dose-dependent manner in DU-145 and LNCaP. In contrast, SIO treatment induced strong Sub G1 and G0/G1 phase cell cycle arrest in a dose-dependent manner in PC-3. SIO exposure for 24 h decreased the expression of the anti-apoptotic protein Bcl-2 and increased the expression of the apoptogenic protein Bax. Moreover, the Bax/Bcl-2expression ratio was increased. Concurrently, the expression of caspase-3 was upregulated. These data support our hypothesis that SIO has anticarcinogenic properties.  相似文献   

14.
Three new sulfated steroid monoglycosides, leptaochotensosides A–C (1–3), and a new sulfated polyhydroxylated steroid (4) were isolated from the alcoholic extract of the Far Eastern starfish Leptasterias ochotensis. The structures of compounds 1–4 were established by extensive nuclear magnetic resonance (NMR) and electrospray ionization mass spectrometry (ESIMS) analyses and chemical transformations. Although the isolated compounds did not show any apparent cytotoxicity against melanoma RPMI-7951 and breast cancer T-47D cell lines, leptaochotensoside A (1) demonstrated inhibition of T-47D cell colony formation in a soft agar clonogenic assay at nontoxic doses. In addition, this compound decreased the epidermal growth factor (EGF)-induced colony formation of mouse epidermal JB6 Cl41 cells. The cancer preventive action of 1 is realized through regulation of mitogen-activated protein kinase (MAPK) signaling pathway.  相似文献   

15.
Investigation of expression pattern of molecular markers in oral epithelial tissues would help to assess the cell differentiation and proliferation as well as early diagnosis of precancerous and cancerous lesions of the oral cavity. Aim of the present study was to investigate the protective effect of berberine on expression pattern of apoptotic, cell proliferative, inflammatory and angiogenic markers during 7,12-dimethylbenz(a)anthracene (DMBA) induced hamster buccal pouch carcinogenesis. Immunohistochemical staining [p53, Bcl-2, Bax, Proliferating Cell Nuclear Antigen (PCNA) and Vascular Endothelial Growth Factor (VEGF)], Enzyme Linked Immuno Sorbent Assay (ELISA) [c-fos, COX-2, caspase-3 and -9] and Real-Time PCR [Cyclin D1 and NFkappaB] were utilized to assess the expression pattern of molecular markers in DMBA induced hamster buccal pouch carcinogenesis. Over expression of mutant p53, PCNA, Bcl-2 and VEGF were noticed in hamsters treated with DMBA alone. Decreased expression of Bax protein was noticed in hamsters treated with DMBA alone. Increased expression of C-fos, COX-2, NFkappaB and Cyclin D1 and decreased activities of caspase-3 and -9 were also noticed in hamsters treated with DMBA alone. Oral administration ofberberine at a dose of 75 mg kg(-1) b.w. brought back the expression of above mentioned molecular markers to near normal pattern in hamsters treated with DMBA. The present results thus suggest that berberine has potent anti-inflammatory, anti-angiogenic, anti-cell proliferative and apoptosis inducing properties in DMBA induced oral carcinogenesis.  相似文献   

16.
This study was performed to elucidate the anticancer mechanism of a lipid-soluble ginseng extract (LSGE) by analyzing induction of apoptosis and arrest of cell cycle progression using the NCI-H460 human lung cancer cell line. Proliferation of NCI-H460 cells was potently inhibited by LSGE in a dose-dependent manner. The cell cycle arrest at the G0/G1 phase in NCI-H460 cells was induced by LSGE. The percentage of G0/G1 phase cells significantly increased, while that of S phase cells decreased after treatment with LSGE. The expression levels of cyclin-dependent kinase2 (CDK2), CDK4, CDK6, cyclin D3 and cyclin E related to G0/G1 cells progression were also altered by LSGE. In addition, LSGE-induced cell death occurred through apoptosis, which was accompanied by increasing the activity of caspases including caspase-8, caspase-9 and caspase-3. Consistent with enhancement of caspase activity, LSGE increased protein levels of cleaved caspase-3, caspase-8, caspase-9, and poly-ADP-ribose polymerase (PARP). These apoptotic effects of LSGE were inhibited by the pan-caspase inhibitor Z-VAD-fmk. These findings indicate that LSGE inhibits NCI-H460 human lung cancer cell growth by cell cycle arrest at the G0/G1 phase and induction of caspase-mediated apoptosis.  相似文献   

17.
Smenospongine, a sesquiterpene aminoquinone isolated from the marine sponge Dactylospongia elegans, was previously reported by us to induce erythroid differentiation and G1 phase arrest of K562 chronic myelogenous leukemia cells. In this study, we investigated the effect of smenospongine on the cell cycles of other leukemia cells, including HL60 human acute promyelocytic leukemia cells and U937 human histiocytic lymphoma cells by flow cytometric analysis. Smenospongine induced apoptosis dose-dependently in HL60 and U937 cells. The smenospongine treatment increased expression of p21 and inhibited phosphorylation of Rb in K562 cells, suggesting the p21-Rb pathway play an important role in G1 arrest in K562 cells. However, the p21 promoter was not activated by the smenospongine treatment based on a luciferase assay using the transfected K562 cells. Smenospongine might induce p21 expression via another mechanism than transactivation of p21 promoter.  相似文献   

18.
为了解油酸在黄曲霉毒素B1（aflatoxin B1,AFB1）诱发的肝损伤中所起的保护作用,以体外培养的肝细胞（L-02）作为靶细胞,研究油酸的保护机制。设置3组实验：对照组（无处理）、AFB1组（只有AFB1）、油酸组（AFB1和油酸共同处理）,药物处理24h后显微镜观察细胞形态,细胞增殖-毒性检测试剂盒（Cell Counting Kit-8, CCK-8）检测细胞活力,荧光法检测活性氧（reactive oxygen species,ROS）水平,Annexin V-FITC/PI检测细胞凋亡率,蛋白质免疫印迹检测血红素加氧酶-1（heme oxygenase 1,HO-1）、Caspase-3以及Survivin蛋白的表达。采用t检验或单因素方差分析进行统计分析。结果发现：与对照组相比,AFB1暴露能够明显抑制细胞活力（P<0.05）,促进细胞凋亡（P<0.001）,升高ROS水平（P<0.001）;与AFB1组相比,油酸作用后细胞活力显著增加（P<0.01）,细胞凋亡减少（P<0.01）,ROS水平降低（P<0.001）。与AFB1组相比,油酸作用后可显著提高 HO-1（P<0.05）和抑凋亡蛋白Survivin的表达（P<0.05）,降低凋亡蛋白Caspase-3（P<0.01）表达。因此认为油酸对AFB1引发的肝细胞损伤具有保护作用,其机制可能与其通过促进抗氧化酶蛋白HO-1的表达,从而降低氧化应激水平,降低细胞凋亡有关。  相似文献   

19.
In this study, the anti-proliferative effect of ilimaquinone, a sesquiterpene derivative from the marine sponge, in breast cancer cells was investigated. Ilimaquinone inhibited the proliferation of MCF-7 and MDA-MB-231 breast cancer cells with IC50 values of 10.6 μM and 13.5 μM, respectively. Non-tumorigenic human breast epithelial cells were less sensitive to ilimaquinone than breast cancer cells. Flow cytometric and Western blot analysis showed that ilimaquinone induced S-phase arrest by modulating the expression of p-CDC-2 and p21. Ilimaquinone induces apoptosis, which is accompanied by multiple biological biomarkers, including the downregulation of Akt, ERK, and Bax, upregulation of p38, loss of mitochondrial membrane potential, increased reactive oxygen species generation, and induced autophagy. Collectively, these findings suggest that ilimaquinone causes cell cycle arrest as well as induces apoptosis and autophagy in breast cancer cells.  相似文献   

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