Sample records for cantharidin

  1. Experimental study on the inhibitory effect of sodium cantharidinate ...

    African Journals Online (AJOL)

    Backgroud: Cantharidin, and its derivatives can not only inhibit the proliferation of tumor cells, but can also induce tumor cell apoptosis. It shows cantharidin exhibits a wide range of reactivity in anticancer. The objective of this paper was to study the inhibitory effect of sodium cantharidinate on human hepatoma HepG2 cells.

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

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    Zhengyu Huang


    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.

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

    Huang, Zhengyu; Zhang, Yalin


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

    Huang, Zhengyu; Zhang, Yalin


    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. PMID:26035491

  5. Cantharidin biosynthesis in a blister beetle: inhibition by 6-fluoromevalonate causes chemical disarmament. (United States)

    Carrel, J E; Doom, J P; McCormick, J P


    Biosynthesis of cantharidin in a blister beetle, Lytta polita, is effectively inhibited by 6-fluoromevalonate. Inhibition is attributed specifically to the fluorine substituent. Biochemical inhibition has not been demonstrated previously for an arthropod's defensive substance.

  6. 9 Expression in Rats with Acute Spinal Cord Injury by Cantharidin

    African Journals Online (AJOL)

    Purpose: To demonstrate the anti-apoptotic effects of cantharidin in mice with acute spinal cord injury. (ASCI). Methods: In total, 30 ... were obtained from the Shanghai Laboratory .... prevent the development of secondary spinal injury in mice ...

  7. Evaluation of efficacy of mineral oil, charcoal, and smectite in a rat model of equine cantharidin toxicosis. (United States)

    Qualls, H J; Holbrook, T C; Gilliam, L L; Njaa, B L; Panciera, R J; Pope, C N; Payton, M E


    The efficacy of orally administered therapeutics for the treatment of cantharidin intoxication has not been evaluated in controlled studies. To develop a model of acute cantharidin intoxication in laboratory rats and to evaluate in this model the relative efficacy of 3 gastrointestinal therapies used to treat equine cantharidin toxicosis. Sixty-four male Sprague-Dawley rats. A blinded, randomized, controlled study was performed on rats surgically implanted with telemetry transmitters for evaluating heart rate, locomotor activity, and body temperature. Orogastric administration of cantharidin was performed within 15 seconds before administration of mineral oil, activated charcoal, or smectite. Negative control groups received therapeutic agents alone. Urine was collected for cantharidin analysis. Rats were sacrificed 24 hours after intoxication, and tissues were collected for histopathologic evaluation. Data analysis included ANOVA procedures and contingency tables. Six of 8 cantharidin-intoxicated rats treated with mineral oil died; bradycardia and hypothermia developed in the animals of this group 0-8 hours after intoxication. Rats treated with mineral oil had higher urine cantharidin concentrations than rats receiving cantharidin alone or with smectite (P = .04). The most severe hypothermia (30.6°C ± 1.0) developed in rats administered mineral oil at 4-8 hours after intoxication, whereas those treated with charcoal (35.2°C ± 0.8) had mean body temperatures higher than all other treatment groups (P = .03). Survival times in the charcoal (P = .16) and smectite (P = .12) treatment groups were not statistically different from negative controls. Mineral oil is often used in the treatment of equine cantharidin toxicosis. Our findings suggest that mineral oil increases cantharidin absorption, worsening morbidity and fatality in rats. Copyright © 2013 by the American College of Veterinary Internal Medicine.

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

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    Chen-Hsi Hsieh


    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.

  9. Interferon-Gamma and Interlukin-4 Patterns in BALB/c Mice Suffering From Cutaneous Leishmaniasis Treated With Cantharidin


    Maroufi, Yahya; Ghaffarifar, Fatemeh; Dalimi, Abdolhosein; Sharifi, Zohreh


    Background: Cutaneous leishmaniasis is a health problem in the world. Lesions should be treated on cosmetically or functionally important sites, such as the face and hands. Cantharidin is a terpenoid compound produced naturally by beetles of Meloidae and Oedemeridae families. Objectives: The current study aimed to investigate the effect of cantharidin on Cutaneous Leishmaniasis (CL) lesions and IFN-γ and IL-4 patterns in infected BALB/c mice. Materials and Methods: Infected BALB/c mice were d...

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

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    Ya Lin Zhang


    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.

  11. Cantharidin Induced Oral Squamous Cell Carcinoma Cell Apoptosis via the JNK-Regulated Mitochondria and Endoplasmic Reticulum Stress-Related Signaling Pathways.

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    Chin-Chuan Su

    Full Text Available Oral cancer is a subtype of head and neck cancer which represents 2.65% of all human malignancies. Most of oral cancer is histopathologically diagnosed as oral squamous cell carcinoma (OSCC. OSCC is characterized by a high degree of local invasion and a high rate of metastasis to the cervical lymph nodes. How to prevention and treatment of OSCC is important and imperative. Here, we investigated the therapeutic effect and molecular mechanism of cantharidin, an active compound isolated from blister beetles, on OSCC in vitro. Results showed that cantharidin significantly decreased cell viability in human tongue squamous carcinoma-derived SAS, CAL-27, and SCC-4 cell lines. The further mechanistic studies were carried out in SAS cells. Cantharidin also significantly increased apoptosis-related signals, including caspase-9, caspase-7 and caspase-3 proteins. Besides, cantharidin decreased mitochondrial transmembrane potential (MMP and induced cytochrome c and apoptosis inducing factor (AIF release. Cantharidin also increased Bax, Bid, and Bak protein expressions and decreased Bcl-2 protein expression. Cantharidin could also increase the endoplasmic reticulum (ER stress signals, including the expressions of phosphorylated eIF-2α and CHOP, but not Grp78 and Grp94. Furthermore, cantharidin reduced pro-caspase-12 protein expression. In signals of mitogen-activated protein kinases, cantharidin increased the phosphorylation of JNK, but not ERK and p38. Transfection of shRNA-JNK to OSCC cells effectively reversed the cantharidin-induced cell apoptotic signals, including the mitochondrial and ER stress-related signaling molecules. Taken together, these findings suggest that cantharidin induces apoptosis in OSCC cells via the JNK-regulated mitochondria and ER stress-related signaling pathways.

  12. Lethal and sublethal effects of cantharidin on the life history traits and population parameters of Helicoverpa armigera (Hübner) (Lepidoptera: Noctuidae). (United States)

    Khan, Rashid A; Rashid, Maryam; Wang, Dun; Zhang, Ya-Lin


    The cotton bollworm, Helicoverpa armigera (Hübner), is a serious and cosmopolitan pest of many economic crops. Its control has not been adequate owing to its resistance to many groups of insecticides. Toxicity of cantharidin on armyworm and diamondback moth has already been reported. However, its toxicity on H. armigera has not been investigated previously. In this study, lethal and sublethal effects of cantharidin on H. armigera under laboratory conditions are reported. Results showed gross abnormalities in the population parameters of H. armigera, ranging from larvae to adults. Reduction in larval weight and wing malformation were observed in the cantharidin-treated population cohort, and higher mortality at the larval, pupal and adult stages was observed in cantharidin-treated H. armigera compared with the control. Moreover, almost 5 times less fecundity was recorded in the treated population cohort. Fertility was also severely affected, and reduction in all population parameters was observed. Cantharidin caused larval mortality and other serious abnormalities in H. armigera population parameters, and therefore may have positive implications for pest management decision-making process. More interestingly, the experiment revealed that cantharidin in sublethal dose mimicked insect growth regulator insecticides. Furthermore, cantharidin could be used as a precursor compound for the synthesis of new analogues and compounds to replace ineffective older compounds. © 2013 Society of Chemical Industry.

  13. Cantharidin Inhibits the Growth of Triple-Negative Breast Cancer Cells by Suppressing Autophagy and Inducing Apoptosis in Vitro and in Vivo

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    Hong-chang Li


    Full Text Available Background/Aims: Cantharidin, a type of terpenoid secreted by the blister beetle Mylabris phalerata (Pallas, has attracted great attention in cancer therapy because of its potential anti-cancer activities. Here, we report the effects on apoptosis and autophagy in human triple-negative breast cancer (TNBC cell lines after treatment with cantharidin and attempt to elucidate the underlying mechanisms. Methods: MDA-MB-231 and MDA-MB-468 cells were treated with cantharidin and cell proliferation was examined using CCK-8 and clone formation assays. The expression of apoptosis- and autophagy-associated proteins was detected by western blotting. Cells were infected with lentivirus carrying the Beclin-1 gene, and MDA-MB-231-beclin1 (MB231-Bec and MDA-MB-468-beclin-1(MB468-Bec cells stably expressing Beclin-1 were established. Autophagic vacuoles in cells were observed with LC3 staining using fluorescence microscopy, and apoptotic cells were detected via flow cytometry. Tumor growth was assessed by subcutaneous inoculation of TNBC cells into BALB/c nude mice. Results: Cantharidin inhibited the proliferation of MDA-MB-231 and MDA-MB-468 cells, and induced cell apoptosis. Cantharidin additionally inhibited the conversion of LC3 I to LC3 II and autophagosome formation by suppressing the expression of Beclin-1. Furthermore, overexpression of Beclin-1 in TNBC cells attenuated the cytotoxicity of cantharidin. In vivo, cantharidin inhibited the growth of MDA-MB-231 and MDA-MB-468 xenografts in nude mice by suppressing autophagy and inducing apoptosis, and Beclin-1 overexpression in TNBC cells reduced the efficacy of cantharidin. Conclusions: Cantharidin inhibits autophagy by suppressing Beclin-1 expression and inducing apoptosis of TNBC cells in vitro and in vivo, thereby representing a potential strategy for the treatment of TNBC.

  14. Suppressions of Migration and Invasion by Cantharidin in TSGH-8301 Human Bladder Carcinoma Cells through the Inhibitions of Matrix Metalloproteinase-2/-9 Signaling

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    Yi-Ping Huang


    Full Text Available Cancer metastasis becomes an initial cause of cancer death in human population. In many cancers, it has been shown that the high levels of matrix metalloproteinase (MMP-2 and/or MMP-9 are associated with the invasive phenotypes of cancer cells. In this study, we investigated the effects of cantharidin, a derivative of blister beetles which is one of the traditional Chinese medicines, on the adhesion, migration, and invasion of human bladder cancer TSGH-8301 cells. Cantharidin effectively suppressed TSGH-8301 cell adhesion, migration, and invasion in a concentration-dependent manner. Results from Western blotting, RT-PCR, and gelatin zymography assays indicated that cantharidin blocked the protein levels, gene expression (mRNA, and activities of MMP-2 and -9 in TSGH-8301 cells. Cantharidin also significantly suppressed the protein expressions of p-p38 and p-JNK1/2 in TSGH-8301 cells. Taken together, cantharidin was suggested to present antimetastatic potential via suppressing the levels of MMP-2 and MMP-9 expression that might be mediated by targeting the p38 and JNK1/2 MAPKs pathway in TSGH-8301 human bladder cancer cells.

  15. Liposomes equipped with cell penetrating peptide BR2 enhances chemotherapeutic effects of cantharidin against hepatocellular carcinoma. (United States)

    Zhang, Xue; Lin, Congcong; Lu, Aiping; Lin, Ge; Chen, Huoji; Liu, Qiang; Yang, Zhijun; Zhang, Hongqi


    A main hurdle for the success of tumor-specific liposomes is their inability to penetrate tumors efficiently. In this study, we incorporated a cell-penetrating peptide BR2 onto the surface of a liposome loaded with the anticancer drug cantharidin (CTD) to create a system targeting hepatocellular carcinoma (HCC) cells more efficiently and effectively. The in vitro cytotoxicity assay comparing the loaded liposomes' effects on hepatocellular cancer HepG2 and the control Miha cells showed that CTD-loaded liposomes had a stronger anticancer effect after BR2 modification. The cellular uptake results of HepG2 and Miha cells further confirmed the superior ability of BR2-modified liposomes to penetrate cancer cells. The colocalization study revealed that BR2-modified liposomes could enter tumor cells and subsequently release drugs. A higher efficiency of delivery by BR2 liposomes as compared to unmodified liposomes was evident by evaluation of the HepG2 tumor spheroids penetration and inhibition. The biodistribution studies and anticancer efficacy results in vivo showed the significant accumulation of BR2-modified liposomes into tumor sites and an enhanced tumor inhibition. In conclusion, BR2-modified liposomes improve the anticancer potency of drugs for HCC.

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

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    Liu, Rong; Cheng, Zhengjun, E-mail:; Li, Tian; Jiang, Xiaohui


    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.

  17. Cantharidin and Occlusion in Verruca Epithelium (United States)


    Common Wart; Warts Hand; Warts; Papillomavirus Infections; DNA Virus Infections; Skin Diseases, Viral; Skin Diseases, Infectious; Skin Diseases; Virus Diseases; Tumor Virus Infections; Verruca Vulgaris; Verruca

  18. Males of a strongly polygynous species consume more poisonous food than females.

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    Carolina Bravo

    Full Text Available We present evidence of a possible case of self-medication in a lekking bird, the great bustard Otis tarda. Great bustards consumed blister beetles (Meloidae, in spite of the fact that they contain cantharidin, a highly toxic compound that is lethal in moderate doses. In addition to anthelminthic properties, cantharidin was effective against gastrointestinal bacteria that cause sexually-transmitted diseases. Although both sexes consumed blister beetles during the mating season, only males selected them among all available insects, and ingested more and larger beetles than females. The male-biased consumption suggests that males could use cantharidin to reduce their parasite load and increase their sexual attractiveness. This plausibly explains the intense cloaca display males perform to approaching females, and the meticulous inspection females conduct of the male's cloaca, a behaviour only observed in this and another similar species of the bustard family. A white, clean cloaca with no infection symptoms (e.g., diarrhoea is an honest signal of both, resistance to cantharidin and absence of parasites, and represents a reliable indicator of the male quality to the extremely choosy females. Our results do not definitely prove, but certainly strongly suggest that cantharidin, obtained by consumption of blister beetles, acts in great bustards as an oral anti-microbial and pathogen-limiting compound, and that males ingest these poisonous insects to increase their mating success, pointing out that self-medication might have been overlooked as a sexually-selected mechanism enhancing male fitness.

  19. Norcantharidin (NCTD) induces mitochondria mediated apoptosis in ...

    African Journals Online (AJOL)

    Norcantharidin (NCTD), a demethylated form of cantharidin, is now in used as a routine anticancer drug. However, the detailed mechanisms underlying this process are generally unclear. The aims of this study were to evaluate the apoptotic effects and molecular mechanisms of NCTD. MTT assay was used to determine the ...

  20. Canthariphilous insects in east Africa | Hemp | Journal of East ...

    African Journals Online (AJOL)

    Canthariphilous insects, representing three different orders, were attracted to cantharidin baits in the years 1989 to 1999 in Tanzania, Kenya and Uganda. Two Aulacoderus, seven Formicomus, two Mecynotarsus, 11 Notoxus, three Tomoderus and one Cyclodinus, Omonadus, Pseudoleptaleus, Sapintus, and Tenuicomus ...

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

    International Nuclear Information System (INIS)

    Yoon, Zo Eun


    The double tracer study on erythrokinetics was carried out experimentally with radioactive iron( 59 Fe) and chromium ( 51 Cr) 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 ( 51 Cr 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

  2. Sp1 transcriptional activity is up-regulated by phosphatase 2A in dividing T lymphocytes. (United States)

    Lacroix, Isabelle; Lipcey, Carol; Imbert, Jean; Kahn-Perlès, Brigitte


    We have followed Sp1 expression in primary human T lymphocytes induced, via CD2 plus CD28 costimulation, to sustained proliferation and subsequent return to quiescence. Binding of Sp1 to wheat germ agglutinin lectin was not modified following activation, indicating that the overall glycosylation of the protein was unchanged. Sp1 underwent, instead, a major dephosphorylation that correlated with cyclin A expression and, thus, with cell cycle progression. A similar change was observed in T cells that re-entered cell cycle following secondary interleukin-2 stimulation, as well as in serum-induced proliferating NIH/3T3 fibroblasts. Phosphatase 2A (PP2A) appears involved because 1) treatment of dividing cells with okadaic acid or cantharidin inhibited Sp1 dephosphorylation and 2) PP2A dephosphorylated Sp1 in vitro and strongly interacted with Sp1 in vivo. Sp1 dephosphorylation is likely to increase its transcriptional activity because PP2A overexpression potentiated Sp1 site-driven chloramphenicol acetyltransferase expression in dividing Kit225 T cells and okadaic acid reversed this effect. This increase might be mediated by a stronger affinity of dephosphorylated Sp1 for DNA, as illustrated by the reduced DNA occupancy by hyperphosphorylated Sp factors from cantharidin- or nocodazole-treated cells. Finally, Sp1 dephosphorylation appears to occur throughout cell cycle except for mitosis, a likely common feature to all cycling cells.

  3. The epidermal cell kinetic response to ultraviolet B irradiation combines regenerative proliferation and carcinogen associated cell cycle delay

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    Olsen, W.M.; Kirkhus, B. (Oslo Univ. (Norway))


    The cell cycle traverse of epidermal basal cells 24 h after in vivo exposure of ultraviolet B (UVB) irradiation was studied by immunochemical staining of incorporated bromodeoxyuridine (BrdU) and bivariate BrdU/DNA flow cytometric analysis. The results were compared with the cell kinetic patterns following topical application of the skin carcinogen methylnitrosourea (MNU) as well as the skin irritant cantharidin. The cell cycle traverse in hairless mouse epidermis 24 h after in vivo exposure to UVB seemed to be a combination of the cell kinetic effects following chemical skin carcinogens and skin irritants. UVB irradiation induced both a delay in transit time through S phase, probably due to DNA damage and subsequent repair, as well as a reduction in the total cell cycle time consistent with rapid regenerative proliferation. (author).

  4. Aphrodisiacs past and present: a historical review. (United States)

    Sandroni, P


    The drug Viagra (sildenafil) has drawn public attention to aphrodisiacs. The search for such substances dates back millennia. Aphrodisiacs can be classified by their mode of action into 3 types: those that increase (1) libido, (2) potency, or (3) sexual pleasure. Various substances of animal and plant origin have been used in folk medicines of different cultures; some have been identified pharmacologically, allowing for understanding of their mechanisms of action. For increasing libido, ambrein, a major constituent of Ambra grisea, is used in Arab countries. This tricyclic triterpene alcohol increases the concentration of several anterior pituitary hormones and serum testosterone. Bufo toad skin and glands contain bufotenine (and other bufadienolides), a putative hallucinogenic congener of serotonin. It is the active ingredient in West Indian "love stone" and the Chinese medication chan su. The aphrodisiac properties are likely of central origin, as are the other effects of the drug. For increasing potency, Panax ginseng used in traditional Chinese medicine, works as an antioxidant by enhancing nitric oxide synthesis in the endothelium of many organs, including the corpora cavernosa; ginsenosides also enhance acetylcholine-induced and transmural nerve stimulation-activated relaxation associated with increased tissue cyclic guanosine monophosphate, hence the aphrodisiac properties. For increasing sexual pleasure, cantharidin ("Spanish fly") is a chemical with vesicant properties derived from blister beetles, which have been used for millennia as a sexual stimulant. Its mode of action is by inhibition of phosphodiesterase and protein phosphatase activity and stimulation of beta-receptors, inducing vascular congestion and inflammation. Morbidity from its abuse is significant. The ingestion of live beetles (Palembus dermestoides) in Southeast Asia and triatomids in Mexico may have a basis similar to cantharidin. It is of paramount importance for the physician to be

  5. Automorphosis-like growth in etiolated pea seedlings is induced by the application of chemicals affecting perception of gravistimulation and its signal transduction (United States)

    Miyamoto, Kensuke; Hoshino, Tomoki; Hitotsubashi, Reiko; Yamashita, Masamichi; Ueda, Junichi

    Both microgravity conditions in space and simulated microgravity using a 3-dimensional clinostat resulted in: (1) automorphosis of etiolated pea seedlings, (2) epicotyls bending ca. 45° from the vertical line to the direction away from cotyledons, (3) inhibition of hook formation and (4) alternation of growth direction of roots. These facts indicate that the growth and development of etiolated pea seedlings on earth is under the influence of gravistimulation. Lanthanum and gadolinium ions, blockers of stretch-activated mechanosensitive ion channels, induced automorphosis-like epicotyl bending. Cantharidin, an inhibitor of protein phosphatase, also phenocopied automorphosis-like growth. On the other hand, cytochalasin B, cytochalasin D and brefeldin A did not induce automorphological epicotyl bending and inhibition of hook formation, although these compounds strikingly inhibited elongation of etiolated pea epicotyls. These results strongly suggest that stretch-activated mechanosensitive ion channels are involved in the perception of signals of gravistimuli in plants, and they are transduced by protein phosphorylation and dephosphorylation cascades by changing levels of calcium ions. Possible mechanisms to induce automorphosis-like growth in relation to gravity signals in etiolated pea seedlings are discussed.

  6. Molecular Cloning and Characterization of the Calcineurin Subunit A from Plutella xylostella

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    Xi'en Chen


    Full Text Available Calcineurin (or PP2B has been reported to be involved in an array of physiological process in insects, and the calcineurin subunit A (CNA plays a central role in calcineurin activity. We cloned the CNA gene from Plutella xylostella (PxCNA. This gene contains an ORF of 1488 bp that encodes a 495 amino acid protein, showing 98%, and 80% identities to the CNA of Bombyx mori, and humans respectively. The full-length of PxCNA and its catalytic domain (CNA1–341, defined as PxCNα were both expressed in Escherichia coli. Purified recombinant PxCNA displayed no phosphatase activity, whereas recombinant PxCNα showed high phosphatase activity with a Km of 4.6 mM and a kcat of 0.66 S−1 against pNPP. It could be activated at different degrees by Mn2+, Ni2+, Mg2+, and Ca2+. The optimum reaction pH was about 7.5 and the optimum reaction temperature was around 45 °C. An in vitro inhibition assay showed that okadaic acid (OA and cantharidin (CTD competitively inhibited recombinant PxCNα activity with the IC50 values of 8.95 μM and 77.64 μM, respectively. However, unlike previous reports, pyrethroid insecticides were unable to inhibit recombinant PxCNα, indicating that the P. xylostella calcineurin appears not to be sensitive to class II pyrethroid insecticides.

  7. Characterization of protein phosphatase 5 from three lepidopteran insects: Helicoverpa armigera, Mythimna separata and Plutella xylostella.

    Directory of Open Access Journals (Sweden)

    Xi'en Chen

    Full Text Available Protein phosphatase 5 (PP5, a unique member of serine/threonine phosphatases, regulates a variety of biological processes. We obtained full-length PP5 cDNAs from three lepidopteran insects, Helicoverpa armigera, Mythimna separata and Plutella xylostella, encoding predicted proteins of 490 (55.98 kDa, 490 (55.82 kDa and 491 (56.07 kDa amino acids, respectively. These sequences shared a high identity with other insect PP5s and contained the TPR (tetratricopeptide repeat domains at N-terminal regions and highly conserved C-terminal catalytic domains. Tissue- and stage-specific expression pattern analyses revealed these three PP5 genes were constitutively expressed in all stages and in tested tissues with predominant transcription occurring at the egg and adult stages. Activities of Escherichia coli-produced recombinant PP5 proteins could be enhanced by almost 2-fold by a known PP5 activator: arachidonic acid. Kinetic parameters of three recombinant proteins against substrate pNPP were similar both in the absence or presence of arachidonic acid. Protein phosphatases inhibitors, okadaic acid, cantharidin, and endothall strongly impeded the activities of the three recombinant PP5 proteins, as well as exerted an inhibitory effect on crude protein phosphatases extractions from these three insects. In summary, lepidopteran PP5s share similar characteristics and are all sensitive to the protein phosphatases inhibitors. Our results also imply protein phosphatase inhibitors might be used in the management of lepidopteran pests.

  8. Protein phosphatase 5 promotes hepatocarcinogenesis through interaction with AMP-activated protein kinase. (United States)

    Chen, Yao-Li; Hung, Man-Hsin; Chu, Pei-Yi; Chao, Tzu-I; Tsai, Ming-Hsien; Chen, Li-Ju; Hsiao, Yung-Jen; Shih, Chih-Ting; Hsieh, Feng-Shu; Chen, Kuen-Feng


    The serine-threonine protein phosphatase family members are known as critical regulators of various cellular functions, such as survival and transformation. Growing evidence suggests that pharmacological manipulation of phosphatase activity exhibits therapeutic benefits. Ser/Thr protein phosphatase 5 (PP5) is known to participate in glucocorticoid receptor (GR) and stress-induced signaling cascades that regulate cell growth and apoptosis, and has been shown to be overexpressed in various human malignant diseases. However, the role of PP5 in hepatocellular carcinoma (HCC) and whether PP5 may be a viable therapeutic target for HCC treatment are unknown. Here, by analyzing HCC clinical samples obtained from 215 patients, we found that overexpression of PP5 is tumor specific and associated with worse clinical outcomes. We further characterized the oncogenic properties of PP5 in HCC cells. Importantly, both silencing of PP5 with lentiviral-mediated short hairpin RNA (shRNA) and chemical inhibition of PP5 phosphatase activity using the natural compound cantharidin/norcantharidin markedly suppressed the growth of HCC cells and tumors in vitro and in vivo. Moreover, we identified AMP-activated protein kinase (AMPK) as a novel downstream target of oncogenic PP5 and demonstrated that the antitumor mechanisms underlying PP5 inhibition involve activation of AMPK signaling. Overall, our results establish a pathological function of PP5 in hepatocarcinogenesis via affecting AMPK signaling and suggest that PP5 inhibition is an attractive therapeutic approach for HCC. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Recent Advances in Developing Insect Natural Products as Potential Modern Day Medicines

    Directory of Open Access Journals (Sweden)

    Norman Ratcliffe


    Full Text Available 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.

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

    International Nuclear Information System (INIS)

    Olsen, W.M.


    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

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

  12. Identification of multiple small heat-shock protein genes in Plutella xylostella (L.) and their expression profiles in response to abiotic stresses. (United States)

    Chen, Xi'en; Zhang, Yalin


    We identify and characterize 14 small heat-shock protein (sHSP) genes from the diamondback moth (DBM), Plutella xylostella (L.), a destructive pest. Phylogenetic analyses indicate that, except for sHSP18.8 and sHSP19.22, the other 12 DBM sHSPs belong to five known insect sHSP groups. Developmental expression analysis revealed that most sHSPs peaked in the pupal and adult stages. The transcripts of sHSPs display tissue specificity with two exhibiting constitutive expression in four tested tissues. Expression of sHSP18.8 in fourth instar larvae is not induced by the tested abiotic stressors, and unless sHSP21.8 is not sensitive to thermal stress, 12 sHSPs are significantly up-regulated. The messenger RNA (mRNA) levels of all sHSPs are reduced under oxidative stress. Food deprivation leads to significant down-regulation of three sHSPs. The majority of sHSPs show expression variation to various heavy metals, whereas mRNA abundances of sHSP22.1 and sHSP 28.9 are reduced by four heavy metals. The responses of sHSPs to indoxacarb and cantharidin are varied. Beta-cypermethrin and chlorfenapyr exposure results in an increase of 13 sHSP transcripts and a reduction of 12 sHSP transcripts, respectively. These results show that different sHSPs might play distinct roles in the development and regulation of physiological activities, as well as in response to various abiotic stresses of DBM.

  13. Gene signature associated with benign neurofibroma transformation to malignant peripheral nerve sheath tumors.

    Directory of Open Access Journals (Sweden)

    Marta Martínez

    Full Text Available Benign neurofibromas, the main phenotypic manifestations of the rare neurological disorder neurofibromatosis type 1, degenerate to malignant tumors associated to poor prognosis in about 10% of patients. Despite efforts in the field of (epigenomics, the lack of prognostic biomarkers with which to predict disease evolution frustrates the adoption of appropriate early therapeutic measures. To identify potential biomarkers of malignant neurofibroma transformation, we integrated four human experimental studies and one for mouse, using a gene score-based meta-analysis method, from which we obtained a score-ranked signature of 579 genes. Genes with the highest absolute scores were classified as promising disease biomarkers. By grouping genes with similar neurofibromatosis-related profiles, we derived panels of potential biomarkers. The addition of promoter methylation data to gene profiles indicated a panel of genes probably silenced by hypermethylation. To identify possible therapeutic treatments, we used the gene signature to query drug expression databases. Trichostatin A and other histone deacetylase inhibitors, as well as cantharidin and tamoxifen, were retrieved as putative therapeutic means to reverse the aberrant regulation that drives to malignant cell proliferation and metastasis. This in silico prediction corroborated reported experimental results that suggested the inclusion of these compounds in clinical trials. This experimental validation supported the suitability of the meta-analysis method used to integrate several sources of public genomic information, and the reliability of the gene signature associated to the malignant evolution of neurofibromas to generate working hypotheses for prognostic and drug-responsive biomarkers or therapeutic measures, thus showing the potential of this in silico approach for biomarker discovery.

  14. Which are the best Chinese herbal injections combined with XELOX regimen for gastric cancer?: A PRISMA-compliant network meta-analysis. (United States)

    Zhang, Dan; Wu, Jiarui; Wang, Kaihuan; Duan, Xiaojiao; Liu, Shi; Zhang, Bing


    The optimal Chinese herbal injections (CHIs) combined with XELOX regimen for patients with gastric cancer remains elusive. The aim of our network meta-analysis (NMA) is to explore the best options among different CHIs for gastric cancer. PubMed, Embase, the Cochrane Library, the China National Knowledge Infrastructure Database (CNKI), Wan-fang Database, Cqvip Database (VIP), China Biology Medicine disc (CBMdisc) were searched to identify RCTs which focused on CHIs against gastric cancer. The quality assessment of included randomized controlled trials (RCTs) was conducted by the Cochrane risk of bias tool. Standard pair-wise and Bayesian NMAs were performed to compare the efficacy and safety of different CHIs combined with the XELOX regimen via Stata 13.0 and WinBUGS1.4 software. A total of 2316 records were searched, the network of evidence included 26 eligible RCTs involving 13 types of CHIs and 2154 patients. The results suggested that Shenqifuzheng+ XELOX, Huachansu+ XELOX, Kangai+ XELOX, Javanica oil emulsion+ XELOX, Aidi injection+ XELOX might be the optimal treatment for gastric cancer in improving the performance status than using XELOX regimen single, with odds ratios (OR) and 95% confidence intervals (CIs) of 2.74 (1.24, 6.17), 8.27 (1.74, 42.43), 4.28 (1.80, 10.48), 5.14 (1.87, 16.28), 0.20 (0.090, 0.44). At the aspects of ADRs (adverse reactions), Compound Kushen+ XELOX, Lentinan+ XELOX, Xiaoaiping injection+ XELOX could obviously relieve leukopenia than only receiving XELOX regimen, and their ORs and 95% CIs were 5.62 (1.41, 36.24), 8.16 (2.25, 29.43), 5.69 (1.85, 15.77). Furthermore, Disodium cantharidinate and vitamin B6+ XELOX, Shenqifuzheng+ XELOX, Kangai+ XELOX, Lentinan+ XELOX could obviously relieve the nausea and vomiting than receiving the XELOX regimen alone, with ORs and 95% CIs of 5.29 (1.30, 23.96), 2.50 (1.16, 5.26), 2.42 (1.06, 5.63), 9.04 (3.24, 26.73). Nevertheless, CHIs combined with XELOX regimen did not confer higher better clinical

  15. Toxic effects of imidazolium ionic liquids on the green seaweed Ulva lactuca: oxidative stress and DNA damage. (United States)

    Kumar, Manoj; Trivedi, Nitin; Reddy, C R K; Jha, Bhavanath


    The green credentials of ionic liquids (ILs) are being increasingly questioned due to the growing evidence of their toxicity to aquatic ecosystems, although the mechanisms of toxicity are unknown. This study provides insights into the mechanism of toxicity and biological effects of 1-alkyl-3-methylimidazolium bromide [C(n)mim]Br (n = 4 to 16) on the marine macroalga Ulva lactuca. The cell viability of this alga during IL exposure was found to be negatively correlated to the chain length of the alkyl group. The IL ([C(12)mim]Br) exposure triggers the generation of reactive oxygen species (ROS viz. O(2)(•-), H(2)O(2), and OH(•)), damage of the membrane and DNA, and inhibition of antioxidant systems in the alga. The enhanced production of ROS and lipid peroxidation in the alga subjected to LC(50) concentration for 4 days was largely attributed to lipoxygenase (LOX) activity coupled with the induction of two LOX isoforms (~80 kDa and ~55 kDa). Pretreatment of the algal thallus with enzyme inhibitors such as diphenylene iodonium, sodium azide, cantharidin, and oxadiazoloquinoxalin-1-one, prior to [C(12)mim]Br exposure showed the regulation of ROS by the activation of membrane bound NADPH-oxidase and cytochrome oxidase. The IL exposure resulted in the accumulation of n-3 and n-6 fatty acids at 0.5 LC(50) concentration indicating the induction of desaturase enzymes. Furthermore, antioxidant enzyme activities such as superoxide dismutase (SOD), ascorbate peroxidase (APX), and glutathione reductase (GR) were enhanced by 1.3-2.0-fold, while glutathione peroxidase (GSH-Px) diminished, together with a higher regeneration rate of reduced ascorbate and glutathione. The isoforms of antioxidant enzymes, namely, Mn-SOD (~85 kDa), APX (~125 and 45 kDa), and GR (~135 kDa) regulated differentially to IL exposure. The comet assay performed for the first time for seaweeds revealed the significant induction of DNA damage (>50-70% increase in % tail DNA over control) in alga exposed