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Sample records for cantharidin

  1. Cantharidin toxicosis in 2 alpacas

    OpenAIRE

    Simpson, Katharine M.; Streeter, Robert N.; de Souza, Patricia; Genova, Suzanne G.; Morgan, Sandra E.

    2013-01-01

    Two adult alpacas were presented for recumbency and reluctance to rise. Cantharidin toxicosis was suspected based on clinical and ancillary diagnostic findings. The diagnosis was confirmed by gas chromatography-mass spectrometry of gastric contents and urine. Despite medical treatment, neither alpaca survived. Blister beetle toxicosis has not been previously described in camelids. Challenges in treatment of affected ruminants or pseudoruminants are noted.

  2. Inhibitory Effect of Cantharidin on Proliferation of A549 Cells

    Institute of Scientific and Technical Information of China (English)

    WANG Xiao-hua; YIN Yuan-qin; SUI Cheng-guang; MENG Fan-dong; MA Ping; JIANG You-hong

    2007-01-01

    Objective: To study the inhibition of Cantharidin against the proliferation of human lung cancer A549 cells and its mechanism. Methods: MTT assay was employed to determine the inhibition of Cantharidin against proliferation of A549 cells and flow Cytometry was applied to analyze A549 cell cycle and the effect of Cantharidin on cell cycle. Results: Cantharidin showed inhibition against the proliferation of A549 cells, and the inhibition was mediated by blocking A549 cell cycle at G2/M phase significantly. Conclusion: Cantharidin exhibits inhibition against the proliferation of human lung cancer A549 cells.

  3. Chronic Sublethal Effects of Cantharidin on the Diamondback Moth Plutella xylostella (Lepidoptera: Plutellidae

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    Zhengyu Huang

    2015-05-01

    Full Text Available The diamondback moth, Plutella xylostella (Linnaeus (Lepidoptera: Plutellidae, is a major pest of cruciferous vegetables worldwide. Cantharidin, a natural toxin isolated from blister beetles, has been reported to be toxic to P. xylostella. However, little is known on the chronic sublethal effects of cantharidin on this species. In this study, we assessed the changes of susceptibility, development, reproduction and other demographic parameters in both the selected P. xylostella strain (Sub, selected by LC25 cantharidin for consecutive 12 generations and the revertant strain (SubR, derived from the Sub strain without being exposed to cantharidin for 12 generations. Results revealed that the two strains maintained a relatively high-level susceptibility to cantharidin. Severe adverse effects on the population dynamics and fitness in Sub strain were observed. In addition, repeated exposure of P. xylostella to sublethal concentration of cantharidin resulted in negative effects on adult performance and deformities in adults. Although morphologically normal for individuals, the SubR strain exhibited a disadvantage in population growth rate. Our results showed that sublethal concentration of cantharidin exhibited severe negative effects on population growth for longtime. These findings would be useful for assessing the potential effects and risk of cantharidin on P. xylostella and for developing effective integrated pest management.

  4. Evaluation of sodium cantharidinate/vitamin B6 in the treatment of primary liver cancer

    OpenAIRE

    Hejun Shao; Guohu Hong; Xinhua Luo

    2014-01-01

    Objective: The present study evaluated the treatment effectiveness of sodium cantharidinate/vitamin B6 in patient with middle/late stage primary liver cancer. Materials and Methods: A 3-month follow-up study on 104 patients with primary liver cancer was carried out. Regular medication treatment was applied to 41 patients and sodium cantharidinate/vitamin B6 combined with the regular medication was applied to 63 patients. The treatment effectiveness and prognosis were evaluated using the s...

  5. Study on effects of cantharidin on cutaneous leishmaniasis, its mechanism and optimization of the therapeutic modes

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    Fatemeh Maleki

    2015-11-01

    Full Text Available Leishmaniasis is one of the major problems in many countries. Leishmania is flagellated protozoa and causative agent of leishmaniasis which is the most important health problem in many countries especially in developing country. Leishmania major causes cutaneous leishmaniasis (CL. CL is endemic in some part of Iran. Pentavalent antimony compounds are main therapy of CL, they have some side effects due to their toxicity, and also relapse is possible. Cantharidin is terpenoid and vesicant compound that can be found in Meloidae and Oedomeridae family beetles. It was used as treatment to cancer and Wart. It is also apoptosis inducer in various cancer cells. In this study, the effect of 0.5, 1, 2, 5, 10, 20 and 50 µg/ml cantharidin on the L. major promastigotes, non-infected macrophages and infected macrophages with parasite amastigotes was studied by (3-(4,5-dimethyl thiazolyl-2-2,5-diphenyle tetrazolium bromide MTT assay and flow cytometer in vitro. The Effect of cantharidin as 0.5, 0.05 and 0.1% ointment surveyed on the Leishmania lesions in BALB/C as well as. Parasite load as determined by Real Time PCR, and IFN-γ and IL-4 was involved by ELISA. Results showed that the highest cytotoxicity (56.14% in promastigotes was in a group that treated with 50 µg/ml cantharidin after 48h. The rate in non-infected macrophages and infected macrophages was 13.05 % and 30.17% respectively. Maximum cytotoxicity rate in promastigotes treated with 50 µg/ml cantharidin after 72 h was determined 66.48%, 48.52% in non- infected macrophages and 62.24% in infected macrophages after 48h by flow cytometry. Group treated with 0.05% cantharidin had lowest rate of ulcer growth. Ulcer size was increased in group treated with 0.5% cantharidin. IFN-γ value in group treated with cantharidin was less than it in untreated (control group, but IL -4 didn’t change. Cantharidin through blister formation induces inflammatory reaction and neutrophils and macrophages infiltration

  6. Norcantharidin, Derivative of Cantharidin, for Cancer Stem Cells

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    Chen-Hsi Hsieh

    2013-01-01

    Full Text Available Cancer stem cells (CSCs existing in human cancers have been demonstrated to be a major cause of cancer treatment resistance, invasion, metastasis, and relapse. Self-renewal pathways, Wnt/β-catenin, Sonic hedgehog (Shh, and the Notch signaling pathway play critical roles in developing CSCs and lead to angiogenesis, migration, invasion, and metastasis. Multidrug resistance (MDR is an unfavorable factor causing the failure of treatments against cancer cells. The most important and thoroughly studied mechanism involved in MDR is the active efflux of chemotherapeutic agents through membrane drug transporters. There is growing evidence that Norcantharidin (NCTD, a water-soluble synthetic small molecule derivative of naturally occurring cantharidin from the medicinal insect blister beetle (Mylabris phalerata Pallas, is capable of chemoprevention and tumor inhibition. We summarize investigations into the modulation of self-renewal pathways and MDR in CSCs by NCTD. This review may aid in further investigation of using NCTD to develop more effective strategies for cancer treatment to reduce resistance and recurrence.

  7. Treatment of mid-late stage NSCLC using sodium cantharidinate/vitamin B6/GP regimen in clinic

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    Baoli Wang

    2014-01-01

    Conclusion: Sodium cantharidinate/vitamin B6/GP regimen had fair effectiveness and synergistically improved the clinical outcomes. It lowered the toxic/adverse effects and its application is worth further investigation and promotion.

  8. Scutellaria baicalensis Alleviates Cantharidin-Induced Rat Hemorrhagic Cystitis through Inhibition of Cyclooxygenase-2 Overexpression

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    Li-Chun Lin

    2012-05-01

    Full Text Available Cantharidin, an active component in mylabris, is used in traditional Chinese medicine (TCM to treat scabies and hepatoma, but accompanied by hemorrhagic cystitis. Evidence shows that cantharidin induces human bladder carcinoma cell death through COX-2 overexpression in vitro. In TCM, Scutellaria baicalensis is usually used to cure mylabris-induced hematuria. This work was undertaken to determine the mechanisms of cantharidin-induced rat hemorrhagic cystitis and explore the uroprotective effect of S. baicalensis. In vitro results showed cantharidin could induce cytotoxicity through prostaglandin (PGE2 overproduction of T24 cells. Boiling-water extract of S. baicalensis (SB-WE could significantly inhibit PGE2 production and COX-2 expression in lipo-polysaccharide-induced RAW 264.7 cells, indicating obvious anti-inflammatory abilities. In vivo results indicated that cantharidin caused rat hemorrhagic cystitis with hematuria via c-Fos and COX-2 overexpression. SB-WE was given orally to cantharidin-treated rats, whereby hematuria level, elevated PGE2 and COX-2 protein overexpression were significantly and dose-dependently inhibited by SB-WE. The anti-inflammatory components of SB-WE are baicalin and wogonin, whose contents were 200.95 ± 2.00 and 31.93 ± 0.26 μg/mg, respectively. In conclusion, cantharidin induces rat cystitis through c-Fos and COX-2 over-expression and S. baicalensis can prevent the resulting hematuria because of its anti-inflammatory effects.

  9. Evaluation of sodium cantharidinate/vitamin B6 in the treatment of primary liver cancer

    Directory of Open Access Journals (Sweden)

    Hejun Shao

    2014-01-01

    Full Text Available Objective: The present study evaluated the treatment effectiveness of sodium cantharidinate/vitamin B6 in patient with middle/late stage primary liver cancer. Materials and Methods: A 3-month follow-up study on 104 patients with primary liver cancer was carried out. Regular medication treatment was applied to 41 patients and sodium cantharidinate/vitamin B6 combined with the regular medication was applied to 63 patients. The treatment effectiveness and prognosis were evaluated using the statistical methods. Results: At the end of the treatment, no significant difference was detected between the two groups; 1-month follow-up survey showed that in the treatment group, the death rate was lower, the treatment gain was maintained longer and the tumor morphology was maintained better, compared with the control group; 3-month follow-up study showed that there was not significance difference between the two groups. Conclusion: Sodium cantharidinate/vitamin B6 might be used as auxiliary drug in patients with primary liver cancer and could improve the treatment outcomes for a short-term period.

  10. Cantharidin Impedes Activity of Glutathione S-Transferase in the Midgut of Helicoverpa armigera Hübner.

    Science.gov (United States)

    Khan, Rashid Ahmed; Liu, Ji Yuan; Rashid, Maryam; Wang, Dun; Zhang, Ya Lin

    2013-01-01

    Previous investigations have implicated glutathione S-transferases (GSTs) as one of the major reasons for insecticide resistance. Therefore, effectiveness of new candidate compounds depends on their ability to inhibit GSTs to prevent metabolic detoxification by insects. Cantharidin, a terpenoid compound of insect origin, has been developed as a bio-pesticide in China, and proves highly toxic to a wide range of insects, especially lepidopteran. In the present study, we test cantharidin as a model compound for its toxicity, effects on the mRNA transcription of a model Helicoverpa armigera glutathione S-transferase gene (HaGST) and also for its putative inhibitory effect on the catalytic activity of GSTs, both in vivo and in vitro in Helicoverpa armigera, employing molecular and biochemical methods. Bioassay results showed that cantharidin was highly toxic to H. armigera. Real-time qPCR showed down-regulation of the HaGST at the mRNA transcript ranging from 2.5 to 12.5 folds while biochemical assays showed in vivo inhibition of GSTs in midgut and in vitro inhibition of rHaGST. Binding of cantharidin to HaGST was rationalized by homology and molecular docking simulations using a model GST (1PN9) as a template structure. Molecular docking simulations also confirmed accurate docking of the cantharidin molecule to the active site of HaGST impeding its catalytic activity. PMID:23528854

  11. Cantharidin Impedes Activity of Glutathione S-Transferase in the Midgut of Helicoverpa armigera Hübner

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    Ya Lin Zhang

    2013-03-01

    Full Text Available Previous investigations have implicated glutathione S-transferases (GSTs as one of the major reasons for insecticide resistance. Therefore, effectiveness of new candidate compounds depends on their ability to inhibit GSTs to prevent metabolic detoxification by insects. Cantharidin, a terpenoid compound of insect origin, has been developed as a bio-pesticide in China, and proves highly toxic to a wide range of insects, especially lepidopteran. In the present study, we test cantharidin as a model compound for its toxicity, effects on the mRNA transcription of a model Helicoverpa armigera glutathione S-transferase gene (HaGST and also for its putative inhibitory effect on the catalytic activity of GSTs, both in vivo and in vitro in Helicoverpa armigera, employing molecular and biochemical methods. Bioassay results showed that cantharidin was highly toxic to H. armigera. Real-time qPCR showed down-regulation of the HaGST at the mRNA transcript ranging from 2.5 to 12.5 folds while biochemical assays showed in vivo inhibition of GSTs in midgut and in vitro inhibition of rHaGST. Binding of cantharidin to HaGST was rationalized by homology and molecular docking simulations using a model GST (1PN9 as a template structure. Molecular docking simulations also confirmed accurate docking of the cantharidin molecule to the active site of HaGST impeding its catalytic activity.

  12. De Novo Transcriptome and Expression Profile Analysis to Reveal Genes and Pathways Potentially Involved in Cantharidin Biosynthesis in the Blister Beetle Mylabris cichorii.

    Science.gov (United States)

    Huang, Yi; Wang, Zhongkang; Zha, Shenfang; Wang, Yu; Jiang, Wei; Liao, Yufeng; Song, Zhangyong; Qi, Zhaoran; Yin, Youping

    2016-01-01

    The dried body of Mylabris cichorii is well-known Chinese traditional medicine. The sesquiterpenoid cantharidin, which is secreted mostly by adult male beetles, has recently been used as an anti-cancer drug. However, little is known about the mechanisms of cantharidin biosynthesis. Furthermore, there is currently no genomic or transcriptomic information for M. cichorii. In this study, we performed de novo assembly transcriptome of M. cichorii using the Illumina Hiseq2000. A single run produced 9.19 Gb of clean nucleotides comprising 29,247 sequences, including 23,739 annotated sequences (about 81%). We also constructed two expression profile libraries (20-25 day-old adult males and 20-25 day-old adult females) and discovered 2,465 significantly differentially-expressed genes. Putative genes and pathways involved in the biosynthesis of cantharidin were then characterized. We also found that cantharidin biosynthesis in M. cichorii might only occur via the mevalonate (MVA) pathway, not via the methylerythritol 4-phosphate/deoxyxylulose 5-phosphate (MEP/DOXP) pathway or a mixture of these. Besides, we considered that cantharidin biosynthesis might be related to the juvenile hormone (JH) biosynthesis or degradation. The results of transcriptome and expression profiling analysis provide a comprehensive sequence resource for M. cichorii that could facilitate the in-depth study of candidate genes and pathways involved in cantharidin biosynthesis, and may thus help to improve our understanding of the mechanisms of cantharidin biosynthesis in blister beetles. PMID:26752526

  13. 3-hydroxy-3-methyl glutaryl coenzyme A reductase: an essential actor in the biosynthesis of cantharidin in the blister beetle Epicauta chinensis Laporte.

    Science.gov (United States)

    Lü, S; Jiang, M; Huo, T; Li, X; Zhang, Y

    2016-02-01

    Cantharidin (C(10)H(12)O(4)) is a monoterpene defensive toxin in insects involved in chemical defence as well as in courtship and mating behaviours. It is relatively well known in the medical literature because of its high anticancer activity and as an effective therapy for molluscum contagiosum. However, little is known about its biosynthesis pathway in vivo, and no enzyme involved in cantharidin biosynthesis has been identified. The purpose of this study was to identify the crucial enzyme that is involved in the biosynthesis of cantharidin. Using the homology cloning method, a 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMGR) gene, the rate-limiting enzyme in the mevalonate pathway, was cloned from the blister beetle Epicauta chinensis. Quantitative reverse transcription PCR and gas chromatography methods revealed that the HMGR transcripts had a positive correlation with cantharidin production in the beetles (R = 0.891). RNA interference (RNAi) knockdown of HMGR mRNA expression was achieved by microinjection of a specific double-stranded RNA with more than 90% RNAi efficiency, and an apparent decrease of cantharidin production was observed. Furthermore, the HMGR mRNA was greatly upregulated by exogenous juvenile hormone III (JH III), and cantharidin production was also raised in males; however, when injecting the JH III with RNAi of HMGR mRNA at the same time, cantharidin production did not rise. These results demonstrate that HMGR is an essential enzyme in cantharidin biosynthesis in the blister beetle E. chinensis, which further verifies previous research results demonstrating that cantharidin is synthesized de novo by the mevalonate pathway in blister beetles. PMID:26566751

  14. Crystal structures and mutagenesis of PPP-family ser/thr protein phosphatases elucidate the selectivity of cantharidin and novel norcantharidin-based inhibitors of PP5C.

    Science.gov (United States)

    Chattopadhyay, Debasish; Swingle, Mark R; Salter, Edward A; Wood, Eric; D'Arcy, Brandon; Zivanov, Catherine; Abney, Kevin; Musiyenko, Alla; Rusin, Scott F; Kettenbach, Arminja; Yet, Larry; Schroeder, Chad E; Golden, Jennifer E; Dunham, Wade H; Gingras, Anne-Claude; Banerjee, Surajit; Forbes, David; Wierzbicki, Andrzej; Honkanen, Richard E

    2016-06-01

    Cantharidin is a natural toxin and an active constituent in a traditional Chinese medicine used to treat tumors. Cantharidin acts as a semi-selective inhibitor of PPP-family ser/thr protein phosphatases. Despite sharing a common catalytic mechanism and marked structural similarity with PP1C, PP2AC and PP5C, human PP4C was found to be insensitive to the inhibitory activity of cantharidin. To explore the molecular basis for this selectivity, we synthesized and tested novel C5/C6-derivatives designed from quantum-based modeling of the interactions revealed in the co-crystal structures of PP5C in complex with cantharidin. Structure-activity relationship studies and analysis of high-resolution (1.25Å) PP5C-inhibitor co-crystal structures reveal close contacts between the inhibitor bridgehead oxygen and both a catalytic metal ion and a non-catalytic phenylalanine residue, the latter of which is substituted by tryptophan in PP4C. Quantum chemistry calculations predicted that steric clashes with the bulkier tryptophan side chain in PP4C would force all cantharidin-based inhibitors into an unfavorable binding mode, disrupting the strong coordination of active site metal ions observed in the PP5C co-crystal structures, thereby rendering PP4C insensitive to the inhibitors. This prediction was confirmed by inhibition studies employing native human PP4C. Mutation of PP5C (F446W) and PP1C (F257W), to mimic the PP4C active site, resulted in markedly suppressed sensitivity to cantharidin. These observations provide insight into the structural basis for the natural selectivity of cantharidin and provide an avenue for PP4C deselection. The novel crystal structures also provide insight into interactions that provide increased selectivity of the C5/C6 modifications for PP5C versus other PPP-family phosphatases. PMID:27002182

  15. Phylogeographic patterns in New Zealand and temperate Australian cantharidines (Mollusca: Gastropoda: Trochidae: Cantharidinae): Trans-Tasman divergences are ancient.

    Science.gov (United States)

    Donald, Kirsten M; Spencer, Hamish G

    2016-07-01

    Current taxonomic treatments of New Zealand and temperate Australian members of the gastropod subfamily Cantharidinae imply that species on either side of the Tasman Sea are closely related and, in some cases, congeneric. Such a close relationship, however, entails a relatively recent divergence of Australian and New Zealand lineages, which seems inconsistent with what is known about cantharidine larval development in general. In order to address these issues, mitochondrial and nuclear DNA sequences were used to ascertain how cantharidine genera became established over the wide geographical range of temperate Australia and New Zealand, including their subantarctic islands. Our robust and dated phylogenies (based on 16S, COI, 12S and 28S sequences) revealed that Australian and New Zealand species fall into endemic clades that have been separated for, at most, 35million years. This divergence date postdates a vicariant split by around 50million years and we suggest that, once again, long-distance trans-Tasman dispersal has played a pivotal role in molluscan evolution in this part of the world. Our results also show that the current classification requires revision. We recognize three genera (Cantharidus [comprising 2 subgenera: Cantharidus s.str. and Pseudomargarella n. subgen.], Micrelenchus [comprising 2 subgenera: Micrelenchus s.str. and Mawhero] and Roseaplagis n. gen.) for New Zealand cantharidine species. In our dated BEAST tree, these genera form a clade with the endemic Australian Prothalotia and South African Oxystele. Other temperate Australian cantharidines in our study fall into previously recognized genera (Phasianotrochus, Thalotia, Calthalotia), which are all quite distinct from Cantharidus in spite of some authors considering various of them to be possible synonyms. Finally, we remove the Australian genus Cantharidella from the Cantharidinae to the subfamily Trochinae and erect a new genus, Cratidentium n. gen., also in the Trochinae, to accommodate

  16. Identification and Biochemical Characterization of Protein Phosphatase 5 from the Cantharidin-Producing Blister Beetle, Epicauta chinensis

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    Xi'en Chen

    2013-12-01

    Full Text Available Protein phosphatase 5 (PP5 is a unique member of serine/threonine phosphatases which has been recognized in regulation of diverse cellular processes. A cDNA fragment encoding PP5 (EcPP5 was cloned and characterized from the cantharidin-producing blister beetle, E. chinensis. EcPP5 contains an open reading frame of 1500 bp that encodes a protein of 56.89 kDa. The deduced amino acid sequence shares 88% and 68% identities to the PP5 of Tribolium castaneum and humans, respectively. Analysis of the primary sequence shows that EcPP5 has three TPR (tetratricopeptide repeat motifs at its N-terminal region and contains a highly conserved C-terminal catalytic domain. RT-PCR reveals that EcPP5 is expressed in all developmental stages and in different tissues. The recombinant EcPP5 (rEcPP5 was produced in Escherichia coli and purified to homogeneity. The purified protein exhibited phosphatase activity towards pNPP (p-nitrophenyl phosphate and phosphopeptides, and its activity can be enhanced by arachidonic acid. In vitro inhibition study revealed that protein phosphatase inhibitors, okadaic acid, cantharidin, norcantharidin and endothall, inhibited its activity. Further, protein phosphatase activity of total soluble protein extract from E. chinensis adults could be impeded by these inhibitors suggesting there might be some mechanism to protect this beetle from being damaged by its self-produced cantharidin.

  17. Investigation of two blood proteins binding to Cantharidin and Norcantharidin by multispectroscopic and chemometrics methods

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Rong; Cheng, Zhengjun, E-mail: ncczj1112@126.com; Li, Tian; Jiang, Xiaohui

    2015-01-15

    The interactions of Cantharidin/Norcantharidin (CTD/NCTD) with two blood proteins, i.e., bovine serum albumin (BSA) and bovine hemoglobin (BHb), have been investigated by the fluorescence, UV–vis absorption, and FT-IR spectra under imitated physiological condition. The binding characteristics between CTD/NCTD and BSA/BHb were determined by fluorescence emission and resonance light scattering (RLS) spectra. The quenching mechanism of two blood proteins with CTD/NCTD is a static quenching. Moreover, the experimental data were further analyzed based on multivariate curve resolution-alternating least squares (MCR-ALS) technique to obtain the concentration profiles and pure spectra for three species (BSA/BHb, CTD/NCTD and CTD/NCTD–BSA/BHb complexes) which existed in the interaction procedure. The number of binding sites n and binding constants K{sub b} were calculated at various temperatures. The thermodynamic parameters (such as, ΔG, ΔH, and ΔS) for BSA–CTD/NCTD and BHb–CTD/NCTD systems were calculated by the Van’t Hoff equation and also discussed. The distance r between CTD/NCTD and BSA/BHb were evaluated according to Förster no-radiation energy transfer theory. The results of Fourier transform infrared (FT-IR), synchronous fluorescence and three-dimensional fluorescence spectra showed that the conformations of BSA/BHb altered with the addition of CTD/NCTD. In addition, the effects of common ions on the binding constants of BSA–CTD/NCTD and BHb–CTD/NCTD systems were also discussed.

  18. A novel cantharidin analog N-Benzylcantharidinamide reduces the expression of MMP-9 and invasive potentials of Hep3B via inhibiting cytosolic translocation of HuR

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Ji-Yeon; Chung, Tae-Wook; Choi, Hee-Jung [Division of Applied Medicine, School of Korean Medicine, Pusan National University, Yangsan, Gyeongnam (Korea, Republic of); Lee, Chang Hyun [Department of Anatomy, College of Korean Medicine, Woosuk University, Wanju-gun, Jeonbuk (Korea, Republic of); Eun, Jae Soon; Han, Young Taek [College of Pharmacy, Woosuk University, Wanju-gun, Jeonbuk (Korea, Republic of); Choi, Jun-Yong [Department of Internal Medicine, Korean Medicine Hospital, School of Korean Medicine, Pusan National University, Yangsan 626-870 (Korea, Republic of); Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan, Gyeongnam (Korea, Republic of); Kim, So-Yeon; Han, Chang-Woo [Department of Internal Medicine, Korean Medicine Hospital, School of Korean Medicine, Pusan National University, Yangsan 626-870 (Korea, Republic of); Jeong, Han-Sol, E-mail: jhsol33@pusan.ac.kr [Division of Applied Medicine, School of Korean Medicine, Pusan National University, Yangsan, Gyeongnam (Korea, Republic of); Ha, Ki-Tae, E-mail: hagis@pusan.ac.kr [Division of Applied Medicine, School of Korean Medicine, Pusan National University, Yangsan, Gyeongnam (Korea, Republic of); Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan, Gyeongnam (Korea, Republic of)

    2014-05-02

    Highlights: • We examined the inhibition of N-Benzylcantharidinamide on MMP-9-mediated invasion. • Unlike cantharidin, N-Benzylcantharidinamide has very low toxicity on Hep3B cells. • The reduced MMP-9 expression was due to HuR-mediated decrease of mRNA stability. • We suggest N-Benzylcantharidinamide as a novel inhibitor of MMP-9-related invasion. - Abstract: Invasion and metastasis are major causes of malignant tumor-associated mortality. The present study aimed to investigate the molecular events underlying inhibitory effect of N-Benzylcantharidinamide, a novel synthetic analog of cantharidin, on matrix metalloproteinase-9 (MMP-9)-mediated invasion in highly metastatic hepatocellular carcinoma Hep3B cells. In this investigation, among six analogs of cantharidin, only N-Benzylcantharidinamide has the inhibitory action on MMP-9 expression at non-toxic dose. The MMP-9 expression and invasion of Hep3B cells were significantly suppressed by treatment of N-Benzylcantharidinamide in a dose-dependent manner. On the other hand, the transcriptional activity of MMP-9 promoter and nuclear levels of NF-κB and AP-1 as the main transcriptional factors inducing MMP-9 expression were not affected by it although the level of MMP-9 mRNA was reduced by treatment of N-Benzylcantharidinamide. Interestingly, the stability of MMP-9 mRNA was significantly reduced by N-Benzylcantharidinamide-treatment. In addition, the cytosolic translocation of human antigen R (HuR), which results in the increase of MMP-9 mRNA stability through interaction of HuR with 3′-untranslated region of MMP-9 mRNA, was suppressed by treatment of N-Benzylcantharidinamide, in a dose-dependent manner. Taken together, it was demonstrated, for the first time, that N-Benzylcantharidinamide suppresses MMP-9 expression by reducing HuR-mediated MMP-9 mRNA stability for the inhibition of invasive potential in highly metastatic Hep3B cells.

  19. 斑蝥素对小菜蛾体壁组织结构的影响%Effect of cantharidin on the integument structure of Plutella xylostella

    Institute of Scientific and Technical Information of China (English)

    陈利平; 杨宝东; 张志勇; 张爱环; 张民照; 张来喜; 孙淑玲

    2011-01-01

    To investigate the contact toxicity of the natural insect product cantharidin ( C10 H12 04, CTD) against a Lepidopteran insect, the diamondback moth Plutella xylostella ( L. ) , transmission electron microscope (TEM ) images of P. Xylostella larvae were observed at different times after treatment with CTD. Exposure to a sublethal dose of 0. 15 μg/ larva and a medial lethal dose of 0. 3 μg/larva for 12 h and 24 h by topical application to the pronotum gave similar results; larvaes' bodies became dark and they died 12 h after treatment. TEM images of the epidermal cells of treated larvae showed that cell nuclei had aggregated, mitochondria had become distorted with mitochondrial cristae and the mitochondria had become blurred and vacuolizated. The quantity of mitochondria and rough endoplasmic reticulum ( RER) declined 12 h after CTD treatment. These phenomena were also evident 24 h after CTD treatment. These results indicate that CTD did not destroy the cuticle layers but damaged epidermal cells in the insects' integument.%为探究昆虫天然产物斑蝥素( cantharifin,CTD)对鳞翅目昆虫小菜娥Plutella xylostella(L.)的触杀机制,利用透射电子显微镜观察了该物质处理小菜蛾4龄幼虫体壁组织结构的变化.斑蝥素亚致死剂量0.15 μg/头和半致死剂量0.3μg/头点滴处理试虫前胸背板,中毒试虫反映结果类似.处理12 h后中毒试虫虫体发黑,陆续死亡.处理12 h后,体壁细胞细胞核固缩并且边极化,线粒体扭曲,内脊模糊出现空泡化,线粒体和粗面内质网数量下降;处理24 h后,体壁细胞出现的类似处理12 h后的症状,且症状更为明显.结果表明CTD对小菜蛾体壁表皮层组织结构无显著破坏作用,但对体壁细胞有明显的致毒作用.

  20. Disodium Cantharidinate and Vitamin B6 Injection plus Chemotherapy for Non-Small Cell Lung Cancer: A Systematic Review%斑蝥酸钠维生素B6注射液联合化疗治疗非小细胞肺癌的系统评价

    Institute of Scientific and Technical Information of China (English)

    盛蕾; 李岩; 陈健鹏

    2012-01-01

    目的 系统评价斑蝥酸钠维生素B6注射液联合化疗治疗非小细胞肺癌( Non-small cell lung carcinoma,NSCLC)的有效性及安全性.方法 计算机检索Cochrane图书馆临床对照试验资料库、MEDLINE、EMbase、CBM、CNKI、VIP等数据库,检索时限为从1966年至2011年11月,纳入斑蝥酸钠维生素B6注射液联合化疗治疗NSCLC的随机对照试验.由2名评价者独立评价并交叉核对纳入研究质量后,对同质研究采用RevMan 5.1软件进行Meta分析.结果 经筛选,最终纳入8个RCT,共539例受试者.文献质量评价结果显示,8篇均为B级.Meta分析结果表明:与对照组相比,斑蝥酸钠维生素B6注射液能提高NSCLC化疗的有效率[RR=1.32,95%CI( 1.07,1.62)]、临床受益率[RR=1.24,95%CI (1.12,1.37)],改善患者生活质量[RR=2.23,95%CI( 1.55,3.19)]、临床症状[RR=1.55,95%CI( 1.24,1.95)],增加患者体重[RR=2.72,95%CI (1.74,4.25)],并减轻骨髓抑制毒性作用(白细胞下降率)[RR=0.36,95%CI (0.21,0.61)].结论 斑蝥酸钠维生素B6注射液对NSCLC患者接受化疗能起到增效减毒作用.为获得更佳的循证医学证据,建议开展更多大样本、多中心、长期随访的高质量临床随机对照试验.%Objective To systematically evaluate the effectiveness and safety of disodium cantharidinate and vita-rain B6 injection plus chemotherapy compared with chemotherapy alone, in the treatment of non-small cell lung cancer (NSCLC). Methods The Cochrane Library (Issue 1, 2011), MEDLINE (1966 to November 2011), EMbase (1984 to November 2011), CBM (1978 to November 2011), CNKI (1995 to November 2011) and VIP (1989 to November 2011) were searched electronically, and the randomized controlled trials (RCTs) about disodium cantharidinate and vitamin B6 injection plus chemotherapy for NSCLC were included. The quality of the included studies was assessed and crosschecked by two reviewers independently, and meta-analyses were performed for homogeneous

  1. 斑蝥酸钠维生素B6注射液联合奈达铂治疗胸腔积液的疗效分析%Analysis of the efficacy of cantharidin sodium vitamin B6 injection combined with nedaplatin treatment of pleural effusion

    Institute of Scientific and Technical Information of China (English)

    王吉天; 付桂莲

    2013-01-01

    目的 观察斑蝥酸钠维生素B6注射液联合奈达铂胸腔注入治疗恶性胸腔积液的疗效和不良反应.方法 将73例肺癌并发恶性胸腔积液患者随机分为观察组(38例)和对照组(35例),观察组患者用一次性中心静脉引流专用导管胸腔置管闭式引流胸腔积液后,胸腔内注射斑蝥酸钠维生素B6注射液和奈达铂;对照组患者胸腔内仅注射奈达铂.观察组胸腔给药:斑蝥酸钠维生素B6注射液50 ml+生理盐水20ml+奈达铂100 mg;对照组胸腔给药:奈达铂100 mg+生理盐水70 ml.结果 观察组患者的临床总有效率和生活质量改善率均优于对照组(均P<0.05),两组患者不良反应差异无统计学意义(P>0.05).结论 胸腔灌注斑蝥酸钠维生素B6注射液联合奈达铂治疗恶性胸腔积液的疗效优于单用奈达铂,不良反应轻.%Objective To observe the efficacy and adverse reactions of cantharidin sodium vitamin B6 injection combined with nedaplatin pleural injection for the treatment of malignant pleural effusion.Methods 73 cases of lung cancer complicated by patients with malignant pleural effusions,central venous drainage catheter chest tube closed drainage of pleural effusion,given the intrathoracic drug injection,cantharidin sodium vitamin B6 injection combined with of nedaplatin(observation group 38 cases),with nedaplatin only(control group,35 cases).observation Group pleural administration:the cantharides sodium vitamin B6 injection 50ml + saline 20ml + nedaplatin 100mg; control group pleural administration:nedaplatin 100mg + saline 70ml.Results Observation group of patients with clinical total rate of efficiency and improved quality of life was better than in control group (P < 0.05),similar to the two sets of adverse reactions.Conclusions Pleural perfusion the sodium cantharidate vitamin B6 injection in conjunction with nedaplatin treatment of malignant pleural effusion effective than single nedaplatin,and the side effects

  2. [Diffusion of lipid fractions through the barrier of cantharidin blisters in hyperlipidemias under conditions of clofibrate and rutinosid interaction].

    Science.gov (United States)

    Szamer, B

    1993-01-01

    Diffusion of lipid fractions from blood to fluid in blister induced by cantharidal ointment, applied on the forearm skin, was studied in 54 patients, thereof 18 with normlipidemia, 13 having type II hyperlipidemia, 23 with type IV hyperlipidemia. Concentrations of triglycerides, phospholipids, free fatty acids, total cholesterol, HDL-cholesterol and LDL--cholesterol were studied in blood and fluid before treatment, 10 days after applying clofibrate, 20 days after clofibrate application, and 10 days following the application of rutinosid, i.e. upon completion of therapy. After the treatment it was observed that in all the patients the concentration of lipid fractions in blood was lowered, except for HDL-cholesterol, the level of which was elevated, as was the concentration of all the fractions in the blister fluid. Lipid concentration in serum, with the exception of free fatty acids, was invariably higher than in blister fluid. Free fatty acids, LDL-cholesterol and HDL-cholesterol diffused from blood to fluid in a greater percentage. Lipid fraction concentration in fluid depended mainly on the concentration of HDL-cholesterol and triglycerides in the blood. In normlipidemia, the highest percentage of lipid fractions was diffused to blister fluid; the percentage was lower in type IV hyperlipidemia, the lowest being in type II hyperlipidemia. Clofibrate hypolipemia action correlated best with with HDL-cholesterol and triglyceride activity. After the treatment, the elevated diffusion of all the fractions from blood to blister fluid was, in my opinion, consistent with lipid metabolism, venoruton, as vessel tightening drug, may play a protective role in relation to endothelia in hyperlipidemia. PMID:8154625

  3. Determination of cantharidin,nitrogen mustard and minoxidil in nurturing hair products by liquid chromatography-tandem mass spectrometry%育发产品中斑蝥素和氮芥及米诺地尔的液相色谱-联质谱测定法

    Institute of Scientific and Technical Information of China (English)

    郑磊; 胡小键; 林少彬

    2016-01-01

    目的 建立了育发产品中斑蝥素、氮芥和米诺地尔的液相色谱-串联质谱(LC-MS-MS)测定方法.方法 样品经直接稀释1000倍,以95%甲醇(含0.2%氨水)-5%乙腈为流动相进行等度洗脱,选用Waters symmetry C18(4.6 mm×250 mm,5 μm)色谱柱,正离子模式下质谱多反应监测(MRM)模式检测.结果 斑蝥素、氮芥和米诺地尔分别在5.00~500、5.00~1000和0.100~50.0 ng/ml的范围内,所得的回归方程均呈较好的线性关系(r≥0.999),检出限分别为2.0、3.4、0.04μg/g定量下限分别为6.4、11.0、0.10μg/g,回收率在94.5%~104.7%之间,RSD<9%.结论 该方法灵敏度高,选择性强,适用于育发产品中斑蝥素、氮芥和米诺地尔的测定.

  4. 斑蝥酸钠维生素B6联合X射线诱导肝癌细胞HepG2凋亡%Disodium Cantharidinate and Vitamin B6 Injection in combination with radiotherapy induces apoptosis and inhibits proliferation in hepatocellular carcinoma cell line HepG2

    Institute of Scientific and Technical Information of China (English)

    赵航宇; 梁健

    2009-01-01

    目的:探讨斑蝥酸钠维生素B6(艾易舒)注射液联合放射疗法对人肝癌细胞HepG2的抑制作用.方法:采用MTT法观察不同浓度的斑螯酸钠维生素B6注射液,对HepG2生长的影响;斑蝥酸钠维生素B6作用于HepG2细胞24 h后接受不同剂量的X射线照射.克隆形成法检测放射增敏比,Annexin-V FITC/P双染法检测HepG2的早期凋亡.倒置荧光显微镜观察肝癌细胞凋亡的形态学变化.结果:斑蝥酸钠维生素B6组、放疗处理组及斑蝥酸钠维生素B6联合放疗组均对HepG2增殖产生抑制作用,与空白对照相比,斑蝥酸钠维生素B6对HepG2有明显抑制作用.并呈现浓度依赖性特点,斑蝥酸钠维生素B6浓度为5.0 mg,L、作用时间为72 h,斑蝥酸钠维生素B6对HepG2细胞的抑制率最大.斑螯酸钠维生素B6与放疗联合处理组对HepG2的抑制率明显高于单纯斑蝥酸钠维生素B6组和单纯放疗组.提示斑蝥酸钠维生素B6与X射线对HepG2的抑制效果具有协同作用.流式细胞分析显示:2.5 mg/L斑蝥酸钠维生素B6作用于HepG2细胞24 h后,11.15%的肝癌细胞发生凋亡.4 Gy的X射线作用HepG2细胞24 h,10.10%的肝癌细胞发生凋亡.5.0 mg/L斑蝥酸钠维生素B6作用于H印G2细胞24 h后对其行X射线照射,23.75%的细胞发生凋亡.克隆形成实验结果显示,斑蝥酸钠维生素B6可以增强肝癌细胞的放射敏感性.结论:斑蝥酸钠维生素B6能够显著抑制H印G2增殖,诱导HepG2凋亡,增强HepG2对X射线照射的敏感性,具有临床意义.

  5. 高效液相色谱法测定斑蝥素钠维生素B6注射液中维生素B6的含量%Determination of Vitamin B6 in Disodium Cantharidinate and Vitamin B6 Injection by HPLC

    Institute of Scientific and Technical Information of China (English)

    顾秋琴

    2014-01-01

    目的:建立斑蝥酸钠维生素B6注射液中维生素B6含量测定的HPLC法。方法采用waters symmetry C18柱(150mm×4.6mm,5.0μm),流动相为0.04%戊烷磺酸钠(用冰醋酸调节pH值至3.0)-甲醇(88∶12),流速1.0ml•min-1,检测波长291nm,柱温35℃。结果维生素B6在39.33~196.6 mg•L-1的范围内线性关系良好(r=1.0000, n=5),测得平均回收率为99.8%,RSD=0.47%(n=9)。结论本方法简便,准确,专属性强。%Objective To establish an HPLC method for the determination of vitamin C and vitamin B6 in ferrous fumarate granules. Methods The HPLC column was Waters symmetry C18 (150mm×4.6mm,5.0μm);the mobile phase was 0.04% sodium heptanesulfonate solution(the pH was adjusted to 3.0 by acetic acid) - methanol(88∶12);the flow rate was 1.0mL•min-1,the detection wavelength was 291 nm , the column temperature was 35℃. Results The linear of Vitamin B6 was 39.33~196.6mg• L-1(r=1.0000),the average recovery was 99.8% with RSD=0.47%(n=6).Conclusion The method is simple,accurate and sensitive.

  6. Study on the Renal Anemia: Experimental Study in Acute Renal Anemia

    International Nuclear Information System (INIS)

    The double tracer study on erythrokinetics was carried out experimentally with radioactive iron(59Fe) and chromium (51Cr) in rabbits. The 0.1% cantharidin solution and 1% pot. perchlomate solution was given subcutaneously to 20 rabbits respectively. 3 and 6 days after injection, the blood chemistry, urine examination, ferrokinetics and apparent half survival time of RBC were (51Cr T-1/2) determined. Following were the results: 1) Red blood cell hematocrit and hemoglobin values were moderately reduced and B.U.N. and serum creatinine values were slightly increased in the cantharidin group, while B.U.N. and serum creatinine values were within normal limits in the pot. perchlomate group. Reticulocyte values were slightly increased in the cantharidin group, while was normal range in the pot. perchlomate group. 2) Blood chemistry finding was not significant statistically in both experimental groups, but serum iron value was moderately reduced in both group. 3) Plasma volume was unchanged in both group, but red cell volume and whole blood volume were slightly reduced in both groups. 4) Results of ferrokinetics were as follows: i) The plasma iron disappearance rate was delayed in both groups. Plasma iron turnover rate, red cell iron utilization and red cell iron turnover rate were decreased in both groups, and then red cell iron turnover rate was more decreased than plasma iron turnover rate in both groups. Circulating red cell iron was slightly increased in cantharidin group and red cell iron concentration was within normal range in both groups. ii) P.I.T.R.-R.C.I.T. value moderately increased in the cantharidin group and slightly increased in the pot. perchlomate group. Reticulocyte index, red cell iron turnover index, plasma iron turnover index and effective erythropoiesis index were wholly reduced in both groups. iii) The red cell life span was slightly shortened in the cantharidin group while was within normal range in pot. perchlomate group. The pathologic finding of

  7. Apoptosis induced by norcantharidin in human tumor cells

    Institute of Scientific and Technical Information of China (English)

    Zhen Xiao Sun; Qing Wen Ma; Tian De Zhao; Yu Lin Wei; Guang Sheng Wang; Jia Shi Li

    2000-01-01

    @@INTRODUCTION The antitumor activity of norcantharidin (NCTD),the demethylated analogue of cantharidin, was studied in the early 1980s in China. NCTD has no side effects on urinary organs which cantharidin has shown and is easier to synthesize, and it can inhibit the proliferation of several tumor cell lines as well as transplanted tumors. Clinical trials with NCTD as a monotherapeutic agent indicated that NCTD had beneficial effects in patients with different kinds of digestive tract cancers, such as primary hepatoma,carcinomas of esophagus and gastric cancer, but no depressive effect on bone marrow cells. NCTD can increase the white blood cell count by stimulating the bone marrow and has some antagonistic effect against leukopenia caused by other agents. The exact cellular and molecular mechanisms of NCTD on tumor cells have not yet been elucidated to date[1-3].

  8. Pharmacokinetics of cefetamet in plasma and skin blister fluid.

    OpenAIRE

    Zimmerli, W; Sansano, S; Wittke, B

    1996-01-01

    Cefetamet pivoxil is an oral cephalosporin with enhanced affinity for the target penicillin-binding proteins 1 and 3 and an increased stability to beta-lactamases compared with older cephalosporins, such as cefalexin or cefaclor. The pharmacokinetics of cefetamet pivoxil was determined after the seventh and final dose of 500 mg of cefetamet pivoxil in eight healthy volunteers. Concentrations in plasma and cantharidin-induced skin blister fluid were determined by a high-performance liquid chro...

  9. Successful treatment of florid cutaneous warts with intravenous cidofovir in an 11-year-old girl.

    OpenAIRE

    IRVINE, ALAN

    2008-01-01

    Cutaneous warts, commonly seen in children and the immunosuppressed are socially distressing and are often resistant to traditional treatments. Here, we report an 11-year-old girl with bilateral florid verrucous lesions on her hands, feet and chin, which were refractory to a number of standard treatments including cryotherapy, cantharidin preparations, topical salicylic acid, surgical debulking techniques, oral Cimetidine, and topical and intralesional Cidofovir. As the disfiguring lesions ha...

  10. Norcantharidin blocks Wnt/β-catenin signaling via promoter demethylation of WIF-1 in glioma.

    Science.gov (United States)

    Xie, Dajiang; Xie, Jixi; Wan, Yingfeng; Ma, Li; Qi, Xuchen; Wang, Kun; Yang, Shuxu

    2016-04-01

    Glioma is one of the most common primary intracranial tumors, and the prognosis is poor even though much treatment management is employed. Wnt/β-catenin signaling has been reported to be associated with glioma. Norcantharidin (NCTD) is the demethylated analog of cantharidin isolated from blister beetles, and it is reported to possess anticancer activity but less nephrotoxicity than cantharidin. Accordingly, we aimed to investigate NCTD as an anti-neoplastic drug that inhibits the Wnt/β‑catenin pathway via promoter demethylation of Wnt inhibitory factor-1 (WIF-1) in glioma growth in vitro. In the present study, we report that NCTD inhibited cell proliferation, induced apoptosis and cell cycle arrest, and suppressed cell migration and invasion in vitro. Moreover, we observed that the expression levels of WIF-1 mRNA and protein in the NCTD-treated cells were increased significantly compared with these levels in the negative control (NC) cells. Promoter demethylation was observed in the NCTD‑treated cells. In contrast, aberrant methylation was observed in the NC cells. Additionally, more investigation revealed that NCTD suppressed activity of Wnt/β-catenin signaling and transcription of β-catenin/TCF-4. Furthermore, the expression of apoptosis-related proteins Bcl-2 and cleaved caspase-3 indicated significant cell apoptosis. We provide initial evidence that NCTD reactivates WIF-1 from a methylation state, and downregulates canonical Wnt/β-catenin signaling. Our findings revealed that NCTD is effective for glioma in vitro and may be a new therapeutic option in vivo. PMID:26781164

  11. Tattoo removal.

    Science.gov (United States)

    Adatto, Maurice A; Halachmi, Shlomit; Lapidoth, Moshe

    2011-01-01

    Over 50,000 new tattoos are placed each year in the United States. Studies estimate that 24% of American college students have tattoos and 10% of male American adults have a tattoo. The rising popularity of tattoos has spurred a corresponding increase in tattoo removal. Not all tattoos are placed intentionally or for aesthetic reasons though. Traumatic tattoos due to unintentional penetration of exogenous pigments can also occur, as well as the placement of medical tattoos to mark treatment boundaries, for example in radiation therapy. Protocols for tattoo removal have evolved over history. The first evidence of tattoo removal attempts was found in Egyptian mummies, dated to have lived 4,000 years BC. Ancient Greek writings describe tattoo removal with salt abrasion or with a paste containing cloves of white garlic mixed with Alexandrian cantharidin. With the advent of Q-switched lasers in the late 1960s, the outcomes of tattoo removal changed radically. In addition to their selective absorption by the pigment, the extremely short pulse duration of Q-switched lasers has made them the gold standard for tattoo removal. PMID:21865802

  12. Norcantharidin inhibits Wnt signal pathway via promoter demethylation of WIF-1 in human non-small cell lung cancer.

    Science.gov (United States)

    Xie, Junran; Zhang, Yaping; Hu, Xuming; Lv, Ran; Xiao, Dongju; Jiang, Li; Bao, Qi

    2015-05-01

    Wingless-type (Wnt) family of secreted glycoproteins is a group of signal molecules implicated in oncogenesis. Abnormal activation of Wnt signal pathway is associated with a variety of human cancers, including non-small cell lung cancer (NSCLC). Wnt antagonists, such as the secreted frizzled-related protein (SFRP) family, Wnt inhibitory factor-1 (WIF-1) and cerberus, inhibit Wnt signal pathway by directly binding to Wnt molecules. Norcantharidin (NCTD) is known to possess anticancer activity but less nephrotoxicity than cantharidin. In this study, we found that NCTD inhibited cell proliferation, induced apoptosis, arrested cell cycle and suppressed cell invasion/migration in vitro. Additionally, Wnt signal pathway transcription was also suppressed. NCTD treatment blocked cytoplasmic translocation of beta-catenin into the nucleus. Alterations of apoptosis-related proteins, such as Bax, cleaved caspase-3 (pro-apoptotic) and Bcl-2 (anti-apoptotic), had been detected. Furthermore, the expression levels of WIF-1 and SFRP1 were significantly increased in NCTD-treated groups compared with negative control (NC) groups. Abnormal methylation was observed in NC groups, while NCTD treatment promoted WIF-1 demethylation. The present study revealed that NCTD activated WIF-1 via promoter demethylation, inhibiting the canonical Wnt signal pathway in NSCLC, which may present a new therapeutic target in vivo. PMID:25814287

  13. Serine/threonine phosphatases in socioeconomically important parasitic nematodes--prospects as novel drug targets?

    Science.gov (United States)

    Campbell, Bronwyn E; Hofmann, Andreas; McCluskey, Adam; Gasser, Robin B

    2011-01-01

    Little is known about the fundamental biology of parasitic nematodes (=roundworms) that cause serious diseases, affecting literally billions of animals and humans worldwide. Unlocking the biology of these neglected pathogens using modern technologies will yield crucial and profound knowledge of their molecular biology, and could lead to new treatment and control strategies. Supported by studies in the free-living nematode, Caenorhabditis elegans, some recent investigations have provided improved insights into selected protein phosphatases (PPs) of economically important parasitic nematodes (Strongylida). In the present article, we review this progress and assess the potential of serine/threonine phosphatase (STP) genes and/or their products as targets for new nematocidal drugs. Current information indicates that some small molecules, known to specifically inhibit PPs, might be developed as nematocides. For instance, some cantharidin analogues are known to display exquisite PP-inhibitor activity, which indicates that some of them could be designed and tailored to specifically inhibit selected STPs of nematodes. This information provides prospects for the discovery of an entirely novel class of nematocides, which is of paramount importance, given the serious problems linked to anthelmintic resistance in parasitic nematode populations of livestock, and has the potential to lead to significant biotechnological outcomes. PMID:20732402

  14. Focus on Poisonous and Harmful Substances in Children’s Cosmetics and Improvement of Their Quality%关注有毒有害物质,提升儿童化妆品质量

    Institute of Scientific and Technical Information of China (English)

    党华; 谢文缄; 贾芳

    2016-01-01

    The quality of children' s cosmetics in China were studied by detecting the poisonous and harmful substances, including heavy metal, microorganism, methanol, formaldehyde and paraformaldehyde, boric acid and borate, salicylic acid, cantharidin, dioxane in 303 batches of commercial children' s cosmetics. Also, the suggestion of production, supervision and purchase of such kind of products were proposed.%通过对303批次儿童化妆品中重金属、微生物、甲醇、甲醛和多聚甲醛、硼酸和硼酸盐、水杨酸、斑螯素、二噁烷等有毒有害物质的检测,摸查我国儿童化妆品的质量状况,剖析问题儿童化妆品的危害,并针对性地提出生产、监管及消费建议。

  15. ROVE BEETLES (COLEOPTERA, STAPHYLINIDAE AND THEIR MEDICAL IMPORTANCE

    Directory of Open Access Journals (Sweden)

    B. Janbakhsh

    1977-06-01

    Full Text Available Rove beetle dermatitis produced by the family Staphylinidae genus Paederus has world- wide distribution some one hundred species of Paederus have been found, but it is believed that only 30 of these produce dermatitis. Up to 1976 three species of paederus have been found in Iran as: P. fusciped Curtis; P. pietschmanni Bershaner , and P. spectabilis Kraatz . Observations on the biology of Paederus SPP have shown that the greatest activity coincides with a high degree of humidity during the hot season. Some species seem to be attracted to artificial light. The most common pathological feature caused by rose beetles is a viscular dermatitis Eye lesions may occur, but they are the result of spread of the irritant with the fingers, after the insect was crushed on the skin, therefore secondary infection. Experiments have shown that dermatitis only develops when a rove beetle is crushed on the haemolymph. The vesicant substance is pederin which is distinct from cantharidin in terns of its biological, physical, and chemical propertics.

  16. The complete mitochondrial genome of Epicauta chinensis (Coleoptera: Meloidae) and phylogenetic analysis among Coleopteran insects.

    Science.gov (United States)

    Du, Chao; He, Shilin; Song, Xuhao; Liao, Qi; Zhang, Xiuyue; Yue, Bisong

    2016-03-10

    The blister beetle is an important resource insect due to its defensive substance cantharidin, which was widely used in pharmacology and plant protection. We determined the complete mitochondrial genome of Epicauta chinensis Laporte (Coleoptera: Tenebrionoidae: Meloidae). The circular genome is 15,717 bp long, encoding 13 protein-coding genes (PCGs), two ribosomal RNAs and 22 tRNAs and containing a A+T-rich region with gene arrangement identical to other Coleopteran species. Twelve PCGs start with typical ATN codon, while ATP8 gene initiate with GTT for first report in Insecta. All PCGs terminate with conventional stop codon TAA or TAG. All tRNAs in E. chinensis are predicted to fold into typical cloverleaf secondary structure, except tRNA-Ser(AGN), in which the dihydrouracil arm (DHU arm) could not form stable stem-loop structure. The secondary structure of lrRNA and srRNA comprises 48 helices and 32 helices respectively. The 1101 bp A+T-rich region contains a 15 bp poly-T stretch and microsatellite-like repeats rather than large tandem repetitive sequences. Phylogenetic analysis, based on 13 PCGs of 45 Coleopteran species, show that E. chinensis grouped with Tenebrionidae species. It also support the topology of (((Chrysomelidae+Curculionoidea)+(Cucujoidea+Cleroidea))+Tenebrionoidea) within Cucujiformia. PMID:26707213

  17. Recent advances in developing insect natural products as potential modern day medicines.

    Science.gov (United States)

    Ratcliffe, Norman; Azambuja, Patricia; Mello, Cicero Brasileiro

    2014-01-01

    Except for honey as food, and silk for clothing and pollination of plants, people give little thought to the benefits of insects in their lives. This overview briefly describes significant recent advances in developing insect natural products as potential new medicinal drugs. This is an exciting and rapidly expanding new field since insects are hugely variable and have utilised an enormous range of natural products to survive environmental perturbations for 100s of millions of years. There is thus a treasure chest of untapped resources waiting to be discovered. Insects products, such as silk and honey, have already been utilised for thousands of years, and extracts of insects have been produced for use in Folk Medicine around the world, but only with the development of modern molecular and biochemical techniques has it become feasible to manipulate and bioengineer insect natural products into modern medicines. Utilising knowledge gleaned from Insect Folk Medicines, this review describes modern research into bioengineering honey and venom from bees, silk, cantharidin, antimicrobial peptides, and maggot secretions and anticoagulants from blood-sucking insects into medicines. Problems and solutions encountered in these endeavours are described and indicate that the future is bright for new insect derived pharmaceuticals treatments and medicines. PMID:24883072

  18. Norcantharidin induced DU145 cell apoptosis through ROS-mediated mitochondrial dysfunction and energy depletion.

    Science.gov (United States)

    Shen, Bo; He, Pei-Jie; Shao, Chun-Lin

    2013-01-01

    Norcantharidin (NCTD), a demethylated analog of cantharidin derived from blister beetles, has attracted considerable attentions in recent years due to their definitely toxic properties and the noteworthy advantages in stimulating bone marrow and increasing the peripheral leukocytes. Hence, it is worth studying the anti-tumor effect of NCTD on human prostate cancer cells DU145. It was found that after the treatment of NCTD with different concentrations (25-100 μM), the cell proliferation was significantly inhibited, which led to the appearance of micronucleus (MN). Moreover, the cells could be killed in a dose-/time-dependent manner along with the reduction of PCNA (proliferating cell nuclear antigen) expression, destruction of mitochondrial membrane potential (MMP), down-regulation of MnSOD, induction of ROS, depletion of ATP, and activation of AMPK (Adenosine 5'-monophosphate -activated protein kinase) . In addition, a remarkable release of cytochrome c was found in the cells exposed to 100 μM NCTD and exogenous SOD-PEG could eliminate the generation of NCTD-induced MN. In conclusion, our studies indicated that NCTD could induce the collapse of MMP and mitochondria dysfunction. Accumulation of intercellular ROS could eventually switch on the apoptotic pathway by causing DNA damage and depleting ATP. PMID:24367681

  19. Norcantharidin induced DU145 cell apoptosis through ROS-mediated mitochondrial dysfunction and energy depletion.

    Directory of Open Access Journals (Sweden)

    Bo Shen

    Full Text Available Norcantharidin (NCTD, a demethylated analog of cantharidin derived from blister beetles, has attracted considerable attentions in recent years due to their definitely toxic properties and the noteworthy advantages in stimulating bone marrow and increasing the peripheral leukocytes. Hence, it is worth studying the anti-tumor effect of NCTD on human prostate cancer cells DU145. It was found that after the treatment of NCTD with different concentrations (25-100 μM, the cell proliferation was significantly inhibited, which led to the appearance of micronucleus (MN. Moreover, the cells could be killed in a dose-/time-dependent manner along with the reduction of PCNA (proliferating cell nuclear antigen expression, destruction of mitochondrial membrane potential (MMP, down-regulation of MnSOD, induction of ROS, depletion of ATP, and activation of AMPK (Adenosine 5'-monophosphate -activated protein kinase . In addition, a remarkable release of cytochrome c was found in the cells exposed to 100 μM NCTD and exogenous SOD-PEG could eliminate the generation of NCTD-induced MN. In conclusion, our studies indicated that NCTD could induce the collapse of MMP and mitochondria dysfunction. Accumulation of intercellular ROS could eventually switch on the apoptotic pathway by causing DNA damage and depleting ATP.

  20. Comparative Gene Expression Profiling of Benign and Malignant Lesions Reveals Candidate Therapeutic Compounds for Leiomyosarcoma

    Directory of Open Access Journals (Sweden)

    Badreddin Edris

    2012-01-01

    Full Text Available Leiomyosarcoma (LMS is a malignant, soft-tissue tumor for which few effective therapies exist. Previously, we showed that there are three molecular subtypes of LMS. Here, we analyzed genes differentially expressed in each of the three LMS subtypes as compared to benign leiomyomas and then used the Connectivity Map (cmap to calculate enrichment scores for the 1309 cmap drugs in order to identify candidate molecules with the potential to induce a benign, leiomyoma-like phenotype in LMS cells. 11 drugs were selected and tested for their ability to inhibit the growth of three human LMS cell lines. We identified two drugs with in vitro efficacy against LMS, one of which had a strongly negative enrichment score (Cantharidin and the other of which had a strongly positive enrichment score (MG-132. Given MG-132’s strong inhibitory effect on LMS cell viability, we hypothesized that LMS cells may be sensitive to treatment with other proteasome inhibitors and demonstrated that bortezomib, a clinically-approved proteasome inhibitor not included in the original cmap screen, potently inhibited the viability of the LMS cell lines. These findings suggest that systematically linking LMS subtype-specific expression signatures with drug-associated expression profiles represents a promising approach for the identification of new drugs for LMS.

  1. The temporal and spatial pattern of histone H3 phosphorylation at serine 28 and serine 10 is similar in plants but differs between mono- and polycentric chromosomes.

    Science.gov (United States)

    Gernand, D; Demidov, D; Houben, A

    2003-01-01

    Immunolabeling using site-specific antibodies against phosphorylated histone H3 at serine 10 or serine 28 revealed in plants an almost similar temporal and spatial pattern of both post-translational modification sites at mitosis and meiosis. During the first meiotic division the entire chromosomes are highly H3 phosphorylated. In the second meiotic division, like in mitosis, the chromosomes contain high phosphorylation levels in the pericentromeric region and very little H3 phosphorylation along the arms of monocentric species. In the polycentric plant Luzula luzuloides phosphorylation at both serine positions occurs along the whole chromosomes, whereas in monocentric species, only the pericentromeric regions showed strong signals from mitotic prophase to telophase. No phosphorylated serine 10 or serine 28 was detectable on single chromatids at anaphase II resulting from equational segregation of rye B chromosome univalents during the preceding anaphase I. In addition, we found a high level of serine 28 as well as of serine 10 phosphorylation along the entire mitotic monocentric chromosomes after treatment of mitotic cells using the phosphatase inhibitor cantharidin. These observations suggest that histone H3 phosphorylation at serine 10 and 28 is an evolutionarily conserved event and both sites are likely to be involved in the same process, such as sister chromatid cohesion. PMID:14610360

  2. Successful treatment of florid cutaneous warts with intravenous cidofovir in an 11-year-old girl.

    Science.gov (United States)

    Cusack, Caitriona; Fitzgerald, Deborah; Clayton, Timothy M; Irvine, Alan D

    2008-01-01

    Cutaneous warts, commonly seen in children and the immunosuppressed are socially distressing and are often resistant to traditional treatments. Here, we report an 11-year-old girl with bilateral florid verrucous lesions on her hands, feet and chin, which were refractory to a number of standard treatments including cryotherapy, cantharidin preparations, topical salicylic acid, surgical debulking techniques, oral Cimetidine, and topical and intralesional Cidofovir. As the disfiguring lesions had a marked adverse effect on her quality of life, a trial of IV Cidofovir was instituted. We administered five cycles of IV Cidofovir with a 1-week interval between the first and second treatment, followed by 2-week intervals thereafter. This regime was well tolerated and we report dramatic resolution of the lesions with persistent clearance 6 months after completion of the fifth infusion. Resolution of recalcitrant warts with IV Cidofovir has been reported in a limited number of cases. Our experience supports its efficacy in this setting, and to the best of our knowledge this is the first report of successful treatment of cutaneous warts with IV Cidofovir in a pediatric case. PMID:18577053

  3. Treatment of molluscum contagiosum: a brief review and discussion of a case successfully treated with adapelene.

    Science.gov (United States)

    Scheinfeld, Noah

    2007-01-01

    Molluscum contagiosum occur in 2-8 percent of children. This infection is among the most common viral skin infections in children. Although the lesions will resolve spontaneously when puberty, there are several reasons to treat them. The lesions can be cosmetically unappealing. About 10 percent of those with this infection develop a pruritic eczematous eruption. In about 4 percent of children with molluscum, the lesions are numerous and recurrent with no other coexisting immunological problem. Patients who have atopic dermatitis may develop widespread involvement with molluscum. Treatment options include destruction, topical therapy, and oral therapy. Destructive treatment modalities include curettage, cryotherapy, expression or pricking with a sterile needle, electrodesiccation, photodynamic therapy, and laser ablation. Destructive therapy is poorly tolerated in children. Topical medical therapy includes salicylic acid, glycolic acid, tretinoin, tazortene, 5 percent sodium nitrite co-applied daily with 5 percent salicylic acid topical preparations, podofilox, liquefied phenol, tretinoin, cantharidin, and potassium hydroxide. Oral treatment of molluscum includes cimetidine. No therapy is universally effective. I report herein a case of generalized numerous and recurrent molluscum treated with minimal irritation with adapelene. PMID:18328209

  4. 细纹豆芫菁3-羟甲基戊二酰辅酶A-还原酶基因全长cDNA克隆及生物信息学分析%Cloning and bioinformatical analysis of 3-hydroxy-3-methylglutaryl coenzyme A reductase gene from the blister beetle Epicauta mannerheimi ( Coleoptera: Meloidae)

    Institute of Scientific and Technical Information of China (English)

    姜鸣; 霍棠; 吕淑敏; 张雅林

    2012-01-01

    3-Hydroxy-3-methylglutaryl coenzyme A reductase ( HMGR) is a key enzyme of the mevalonate pathway. Obtaining HMGR gene information is the basis of studying the relationship between cantharidin biosynthesis and the mevalonate pathway. In this study, a full-length cDNA of the HMGR gene was cloned from the blister beetle Epicauta mannerheimi ( Maklin) by RACE technology, which was named EmHMGR (GeneBank accession no. JQ690539). The full-length of EmHMGR is 3 118 bp with an ORF of 2 526 bp, containing a 5'-untranslated region (5'-UTR) of 178 bp and a 3'UTR of 414 bp. It encodes a deduced protein of 842-amino acid residues, with a predicted molecular mass of 92.8 kDa and isoeletric point (pI) of 6.0. Its predicted molecular formula is C4135H6604N1098O1216S50. Bioinformatical analysis showed that its instability index is 43. 37 and the GRAVY 0.091, suggesting that EmHMGR is an unstable hydrophobic protein. The deduced protein EmHMGR has the conserved functional domain of HMGR_Class I and the sterol-sensing domain, and shares more than 50% amino acid identity with HMGRs from other insects. Phylogenetic analysis showed that EmHMGR has the closest relationship with HMGRs of chrysomelids. This study provides the basis for further research on the biosynthetic pathway of cantharidin in the blister beetles.%3-羟甲基戊二酰辅酶A-还原酶(3-hydroxy-3-methylglutaryl coenzyme Areductase,HMGR)是甲羟戊酸途径的关键酶.获得芫菁体内HMGR基因信息是确定甲羟戊酸途径与斑蝥素合成相关性的基础.本研究利用RACE技术从细纹豆芫菁Epicauta mannerheimi(M(a)klin)体内克隆获得HMGR基因全长cDNA序列,命名为EmHMGR(GenBank登录号为JQ690539).该基因全长3118 bp,其中5’端非翻译区178 bp,3’端非翻译区414 bp,开放阅读框2 526 bp,编码842个氨基酸.推测的蛋白质分子量为92.8 kDa,理论等电点为6.0,预测分子式为C4135H6604N1098O1216S50,不稳定系数为43.37,总亲水性系数为0.091,为疏水性不

  5. Studies of early effects of ultraviolet B irradiation on hairless mouse epidermis

    International Nuclear Information System (INIS)

    The present study describes various early biochemical and cell kinetic aspects of the acute response of hairless epidermis with irradiation of narrow-banded wavelengths in the ultraviolet B region of the spectrum (280-320 nm), and their possible relationship to ultraviolet carcinogenicity. In vivo exposure of hairless mouse skin to a single dose of various narrow-banded wavelengths of ultraviolet B light demonstrated that 280, 290, 297 and 302 nm had a carcinogenic potency according to the tetrazolium test. No induction of DT-diaphorase was observed, which may signify that the actions of ultraviolet B light and chemical skin carcinogens differ at the cellular level, even though the nuclear effect on DNA may in principle be the same, e.g. mutation events, activation or amplication of oncogens, inhibition of anti-oncogens, etc. The early epidermal cell kinetic after a biologically relevant dose of ultraviolet B irradiation at a wavelength of 297 nm could be divided into two periods: the initial inhibition in the uptake of tritiated thymidine and the mitotic rate were followed by a long-lasting depression in the DNA synthesis rate combined with rapid cell proliferation. This shows that the acute vascular response (erythema and edema) to ultraviolet B lights is also associated with epidermal perturbations similar to the carcinogen-associated delay in cell cycle passage seen after chemical skin carcinogens like 7,12-dimethylbenz(α)anthracene and methylnitrosourea, as well as to the regenerative proliferation observed after chemical skin irritants like cantharidin. 93 refs., 6 figs

  6. Automorphosis of higher plants in space is simulated by using a 3-dimensional clinostat or by application of chemicals

    Science.gov (United States)

    Miyamoto, K.; Hoshino, T.; Hitotsubashi, R.; Yamashita, M.; Ueda, J.

    In STS-95 space experiments, etiolated pea seedlings grown under microgravity conditions in space have shown to be automorphosis. Epicotyls were almost straight but the most oriented toward the direction far from their cotyledons with ca. 45 degrees from the vertical line as compared with that on earth. In order to know the mechanism of microgravity conditions in space to induce automorphosis, we introduced simulated microgravity conditions on a 3-dimensional clinostat, resulting in the successful induction of automorphosis-like growth and development. Kinetic studies revealed that epicotyls bent at their basal region or near cotyledonary node toward the direction far from the cotyledons with about 45 degrees in both seedlings grown on 1 g and under simulated microgravity conditions on the clinostat within 48 hrs after watering. Thereafter epicotyls grew keeping this orientation under simulated microgravity conditions on the clinostat, whereas those grown on 1 g changed the growth direction to vertical direction by negative gravitropic response. Automorphosis-like growth and development was induced by the application of auxin polar transport inhibitors (2,3,5-triiodobenzoic acid, N-(1-naphtyl)phthalamic acid, 9-hydroxyfluorene-9-carboxylic acid), but not an anti-auxin, p-chlorophenoxyisobutyric acid. Automorphosis-like epicotyl bending was also phenocopied by the application of inhibitors of stretch-activated channel, LaCl3 and GdCl3, and by the application of an inhibitor of protein kinase, cantharidin. These results suggest that automorphosis-like growth in epicotyls of etiolated pea seedlings is due to suppression of negative gravitropic responses on 1 g, and the growth and development of etiolated pea seedlings under 1 g conditions requires for normal activities of auxin polar transport and the gravisensing system relating to calcium channels. Possible mechanisms of perception and transduction of gravity signals to induce automorphosis are discussed.

  7. Structural Basis for the Catalytic Activity of Human Serine/Threonine Protein Phosphatase type 5 (PP5)

    Science.gov (United States)

    Swingle, Mark R.; Ciszak, Ewa M.; Honkanen, Richard E.

    2004-01-01

    Serine/threonine protein phosphatase-5 (PP5) is a member of the PPP-gene family of protein phosphatases that is widely expressed in mammalian tissues and is highly conserved among eukaryotes. PP5 associates with several proteins that affect signal transduction networks, including the glucocorticoid receptor (GR)-heat shock protein-90 (Hsp90)-heterocomplex, the CDC16 and CDC27 subunits of the anaphase-promoting complex, elF2alpha kinase, the A subunit of PP2A, the G12-alpha / G13-alpha subunits of heterotrimeric G proteins and DNA-PK. The catalytic domain of PP5 (PP5c) shares 35-45% sequence identity with the catalytic domains of other PPP-phosphatases, including protein phosphatase-1 (PP1), -2A (PP2A), -2B / calcineurin (PP2B), -4 (PP4), -6 (PP6), and -7 (PP7). Like PP1, PP2A and PP4, PP5 is also sensitive to inhibition by okadaic acid, microcystin, cantharidin, tautomycin, and calyculin A. Here we report the crystal structure of the PP5 catalytic domain (PP5c) at a resolution of 1.6 angstroms. From this structure we propose a mechanism for PP5-mediated hydrolysis of phosphoprotein substrates, which requires the precise positioning of two metal ions within a conserved Asp(sup 271)-M(sub 1):M(sub 2)-W(sup 1)-His(sup 304)-Asp(sup 274) catalytic motif. The structure of PP5c provides a possible structural basis for explaining the exceptional catalytic proficiency of protein phosphatases, which are among the most powerful known catalysts. Resolution of the entire C-terminus revealed a novel subdomain, and the structure of the PP5c should also aid development of type-specific inhibitors.

  8. Application of biological pesticides in the control of codling moth, Cydia pomonella (L.)%生物源农药在苹果蠹蛾防治中的应用

    Institute of Scientific and Technical Information of China (English)

    吴正伟; 杨雪清; 张雅林

    2015-01-01

    The codling moth, Cydia pomonella (L.) (Lepidoptera:Tortricidae), a notorious quarantine fruit pest worldwide, poses a serious threat to the main apple producing areas in China. In terms of food safety, environmentally friendly biological pesticides are desirable substitutes for chemical pesticides;the long ̄term use of the latter have caused resistance, preventing its long team use for codling moth control. The present review summarized the use of biological pesticides, including parasitoids, sterilized insect, granu ̄lovirus, entomopathogenic nematodes, Bacillus thuringiensis, entomopathogenic fungi, microsporidia, sex pheromone, cantharidin, and spinosad that have been either applied or suggested to control codling moth. The challenges faced by biological pesticides are al ̄so discussed, and anyhow it will play an important role in the integrated pest management of codling moth due to its characteristics of infinite variety, wide source, good selectivity in application.%苹果蠹蛾是世界性检疫害虫,对我国苹果优势产区构成了巨大威胁。长期依赖化学防治使该虫抗性问题变得十分严峻。为了保障食品安全,以环境友好的生物源农药替代化学农药已成为当前苹果蠹蛾防治的热点。本文对国内外现有的生物源农药,如寄生蜂、不育昆虫、颗粒体病毒、病原线虫、Bt、病原真菌、微孢子虫、性信息素、斑蝥素、多杀菌素等,在苹果蠹蛾防治中的最新应用及其存在的问题进行论述,讨论了生物源农药凭借其种类多、来源广且在用药时期上选择性强等特点,在该虫综合治理中的重要地位及面临的挑战。

  9. 去甲斑蝥素对Burkitt淋巴瘤Raji细胞株生物学特性的影响%Norcantharidin inhibits proliferation of Burkitt lymphoma Raji cells and induces cell cycle arrest

    Institute of Scientific and Technical Information of China (English)

    余莉华; 曾雅莉; 贺艳杰; 胡亮杉; 宋朝阳; 郭坤元

    2012-01-01

    目的:探讨去甲斑蝥素(nor-cantharidin,NCTD)对Raji细胞的增殖抑制及周期阻滞作用.方法:通过台盼蓝拒染法观察NCTD对Raji细胞及外周血单个核细胞(peripheral blood mononuclear cells,PBMC)的增殖抑制情况;甲基纤维素集落形成法观察NCTD对Raji细胞自我更新能力的影响;流式细胞仪检测Raji 细胞周期变化.结果:NCTD抑制Raji细胞增殖,具有剂量时间依赖性(P < 0.05),但是对单个核细胞增殖无影响(P > 0.05);NCTD显著抑制Raji细胞的集落形成能力(P < 0.05),NCTD使 Raji细胞G2/M期细胞增多,G0/G1期细胞和S期细胞减少.结论:去甲斑蝥素能抑制Raji细胞增殖并产生G2/M期阻滞,且对Raji原始干祖细胞有抑制作用,有可能成为一种新的抗瘤制剂作用于人Burkitt淋巴瘤.%Objective To investigate the effects of Norcantharidin (NCTD) on human Burkitt lymphoma cell line Raji proliferation and cell cycle arrest in vitro. Methods Trypan blue assay was used to detect the inhibiting rate of NCTD on Raji cells and peripheral blood mononuclear cells (PBMC), in which concentration of NCTD were different. The self-renewal and proliferating ability were examined by methylcellblose conlony-forming units(CFU) assay. The cell cycle were detected by flow cytometry. Results By using Trypan blue assay, we found that NCTD can inhibit the proliferation of Raji cells significantly in dose- and time-dependant manners (P 0.05). The CFU assay shows that the amount of colony-forming number decreased more in Raji cells administated with NCTD than in Raji cells which were pre-treated with NCTD for 48 h. The proportion of cells at the G2/M stage increased while ones at the G

  10. Effects of Sodium Cantharidate Vitamin B6 on Proliferation,Apoptosis and Influence of NF-κB and Caspase3/7 on Human Lung Cancer A549 Cells%斑蝥酸钠维生素B6注射液对人肺癌细胞系A549增殖抑制及核因子κB和Caspase3/7的影响

    Institute of Scientific and Technical Information of China (English)

    温省初; 王一飞; 李爱明; 李冠军; 成志勇; 王亚丽; 石林

    2011-01-01

    Objective To investigate the effect of sodium cantharidinate ( SC ) vitamin B6 on human non - small cell lung cancer A549 cell proliferation, apoptosis and the influence of transcription factor NF - kB and apoptosis molecules Caspase3/7. Methods Different concentrations of SC vitamin B6 and A549 cells were cultured together; Cells apoptosis was tested by light microscopy and fluorescent staining Hoechst33342 morphology; MTT assay tested cell proliferation; Rhodamine 123 examined mitochondrial membrane potential; Caspase3/7 activity assay kit tested Caspase3/7 activity; Western blot detected of NF - kB P65 , I - kB protein levels. Results SC vitamin B6 inhibited the A549 cells proliferation, of which there were apparent apoptotic morphological changes. When 5. 0 mg/L group roled in A549 cells 72 h, cell proliferation inhibition rate reached 67. 37 percent maximum. Mitochondrial membrane potential results showed that with increasing concentration of SC vitamin B6 and time, the mitochondrial membrane potential gradually weakened, while Caspase3/7 protein activity increased. After SC vitamin B6 was added in A549 cells, NF - kB P65 protein levels was reduced ( P < 0. 05 ) and I - kB protein levels had no changes. Conclusion SC vitamin B6 inhibits the NF - kB P65 expression, activates caspase - 3/7 activities which inhibits A549 cells proliferation and induce apoptosis.%目的 探讨斑蝥酸钠(SC)维生素B6注射液对人非小细胞肺癌A549细胞增殖、凋亡及核因子κB(NF-κB)、凋亡分子Caspase3/7的影响.方法 用不同浓度(0、1.0、2.5、5.0 mg/L)的SC维生素B6注射液处理A549细胞,观察光镜及Hoechst33342荧光染色检测细胞凋亡形态;用噻唑蓝(MTT)比色法检测SC维生素B6注射液对细胞增殖的抑制作用;罗丹明123检测线粒体膜电位;Caspase3/7活性检测试剂盒检测Caspase3/7活性;蛋白印迹检测NF-κB P65、I-κB 蛋白表达.结果 SC维生素B6注射液对A549细胞的体外增殖有明显抑制作