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Douglas W Tallamy - One of the best experts on this subject based on the ideXlab platform.
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Effects of age, sex, and dietary history on response to cucurbitacin in Acalymma vittatum
Entomologia Experimentalis et Applicata, 2002Co-Authors: Rebecca R. Smyth, Douglas W Tallamy, J. Alan A. Renwick, Michael P. HoffmannAbstract:The chrysomelid Acalymma vittatum is stenophagous, subsisting almost entirely on plants in the Cucurbitaceae, which generally contain Cucurbitacins. Cucurbitacins are extremely bitter tetracyclic triterpenoids that are toxic to most organisms. As do other diabroticite beetles, A. vittatum sequester Cucurbitacins, which have been shown to act as phagostimulants and arrestants. Our results reveal, however, that for A. vittatum the response to cucurbitacin diminishes with continued sequestration. Colony-reared A. vittatum were fed only roots (as larvae) and foliage of either `Marketmore 76' (which contains a normal amount of cucurbitacin, `bitter') or `Marketmore 80' (a near isogenic line that contains no cucurbitacin, `non-bitter') cucumber. Over 1200 individual beetles from the day of adult emergence to 15 days following emergence were placed in choice and no-choice arenas containing potted cotyledons of the two cucumber varieties for 24 h. In choice tests, overall preference for the bitter cucumber cultivar was maintained, but degree of preference changed with age and became significantly less for beetles reared on bitter diets. Furthermore, in no-choice tests, age, sex, dietary history, and interactions among these variables all significantly affected the feeding response to cucurbitacin. For A. vittatum reared without cucurbitacin, total consumption of the bitter cultivar increased over time. For beetles reared with cucurbitacin, total foliage consumption of the bitter cultivar declined, within nine days, to equal that of the non-bitter cultivar. Feral A. vittatum , unexpectedly, consumed more of the non-bitter than the bitter cultivar in no-choice tests. Ecological and applied implications of this variation in response to cucurbitacin are discussed.
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male traits under cryptic female choice in the spotted cucumber beetle coleoptera chrysomelidae
Behavioral Ecology, 2002Co-Authors: Douglas W Tallamy, Bradford E Powell, Julie A McclaffertyAbstract:Males of the spotted cucumber beetle (Diabrotica undecimpunctata howardi) rhythmically stroke females with their antennae during copulation. Males that stroke quickly have a higher probability of being accepted as a mate. We determined (1) the mechanism by which females prevent unattractive males from passing spermatophores, (2) whether antennal stroking signals to females the likelihood of receiving a nuptial gift, and (3) if other male traits in addition to stroking are subjected to sexual selection from female preference. Dissections of pairs flash-frozen in copula during and after antennal stroking showed musculature that, when contracted, folded the vaginal duct leading to the female's bursa copulatrix in a way that prevented complete penetration by the aedeagus. These muscles were always contracted while males were stroking and always relaxed after stroking had ceased. Males accepted as mates did not differ from males that failed to pass a spermatophore in either absolute or relative body weight, aedeagus length, or the amount of Cucurbitacins (potential nuptial gifts) sequestered in their spermatophores. Although 99% of the beetles that came to cucurbitacin-rich Cucurbita fruits in the field were males, males that had sequestered Cucurbitacins did not stroke females faster than males with no Cucurbitacins, and fast-stroking males were not more likely to find and sequester Cucurbitacins than were males that stroked more slowly. Males with a cucurbitacin slurry painted on their antennae had no mating advantage over controls. We conclude that females discriminate among males after copulation has begun on the basis of antennal stroking displays (or some trait correlated with stroking speed) that males perform to entice females to relax their bursal sphincter. Copyright 2002.
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Fate of Male-derived Cucurbitacins in Spotted Cucumber Beetle Females
Journal of Chemical Ecology, 2000Co-Authors: Douglas W Tallamy, Piotr M. Górski, Julia K. BurzonAbstract:Using the spotted cucumber beetle, Diabrotica undecimpunctata howardi , as a model species, we begin an examination of the role of dietary Cucurbitacins, the bitter tetracyclic triterpenes produced by cucurbits, in the reproductive behavior of luperine chrysomelids that seek these compounds for purposes other than host-plant recognition or nutrition. By manipulating the cucurbitacin content of adult diets, we determine: (1) how males and females partition Cucurbitacins between reproductive organs and other tissues, (2) the extent to which males pass Cucurbitacins to females during copulation, and (3) if females increase their cucurbitacin stores via multiple matings. After two days of exposure to dietary Cucurbitacins, 8.3 times more Cucurbitacins per gram dry weight were sequestered in male spermatophores than in the aggregate of remaining male tissues. These cucurbitacin-rich spermatophores were passed to females during mating, and 78.8% of the transferred cucurbitacin was deposited in eggs, 11.8% was irreversibly sequestered in other female tissues, and 9.4% was apparently excreted. Females copulated with 0–15 males prior to accepting a complete spermatophere, but did not accept measurable amounts of cucurbitacin from rejected males. Regardless of when it was received, females lost subsequent receptivity to additional males after accepting a complete spermatophore. The implications of these data are discussed in terms of sexual selection hypotheses and mating behavior in cucumber beetles.
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Cucurbitacins: A Role in Cucumber Beetle Steroid Nutrition?
Journal of Chemical Ecology, 1999Co-Authors: Fathi T. Halaweish, Douglas W Tallamy, Eva SantanaAbstract:The conditional role of Cucurbitacins as phytosteroid supplements, cholesterol precursors, or ecdysteroid antagonists in the spotted cucumber beetle, Diabrotica undecimpunctata howardi , was investigated in two ways: by comparing larval survival and growth rate on cucurbitacin-rich and cucurbitacin-poor squash cultivars of Cucurbita pepo and by manipulating the presence of cholesterol, phytosteroids, and Cucurbitacins in an artificial diet and examining the effects on adult survival and fecundity. Larvae that developed on cucurbitacin-rich roots grew significantly faster and survived as well as larvae on cucurbitacin-poor roots. There was no evidence, however, that adults could substitute Cucurbitacins in vital phytosteroid roles. Beetles reared on a cucurbitacin-rich, phytosteroid-poor diet laid significantly fewer eggs and died significantly younger than beetles with a full complement of dietary phytosteroids and also laid fewer eggs than beetles with no access to phytosteroids in their adult diet. The data are consistent with the hypothesis that, when the side chain of dietary Cucurbitacins can be successfully hydrogenated, these compounds play a nutritional role as substitutes or precursors for structural steroids. In contrast, when the carbon–carbon double bond cannot be hydrogenated, Cucurbitacins may become antagonists at ecdysteroid receptors, negatively affecting beetle fitness.
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sequestered Cucurbitacins and pathogenicity of metarhizium anisopliae moniliales moniliaceae on spotted cucumber beetle eggs and larvae coleoptera chrysomelidae
Environmental Entomology, 1998Co-Authors: Douglas W Tallamy, Daryl P Whittington, Ferdinand Defurio, David A Fontaine, Piotr M. Górski, Peter W GothroAbstract:It has long been hypothesized that many luperine cucumber beetles ultimately consume and sequester highly bitter cucurbitacin triterpenes to gain protection from predators and possibly parasitoids. Here we expand this protections hypothesis to include antibiotic protection against entontopathogens. Specifically, we examine the ability of Cucurbitacins sequestered in the eggs and larvae of Diabrotica undercimpunctata howardii Barber, the spotted cucumber beetle, to reduce the pathogenicity of the entomopathogen Metarhizium anisopliae, Bitter and nonbitter eggs and larvae (those with and without sequestered cucurbitacin glycosides) were exposed to 0, 10 3 , 10 5 , and 10 7 M. anisopliae conidia per milliliter of distilled water. A significantly greater percentage of both eggs and larvae contining Cucurbitacins survived exposure to the fungus, suggesting that the adaptive value of cucurbitacin pharmacophagy its cucumber beetles includes an antibiotic benefit.
Fathi T. Halaweish - One of the best experts on this subject based on the ideXlab platform.
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the role of Cucurbitacins in combating cancers a mechanistic review
Pharmacognosy Reviews, 2018Co-Authors: Abdulrhman Alsayari, Fathi T. Halaweish, Narasimman GurusamyAbstract:Cucurbitacins are highly oxidized tetracyclic triterpenoids from the Cucurbitaceae families. Several Cucurbitacins, such as B, D, E, I, R, IIa, and dihydrocucurbitacin B, have been shown to possess antiproliferative and anticancer activities. Mechanistically, Cucurbitacins induce cell cycle arrest at the G2/M phase and induce apoptosis through several mechanisms, such as the production of reactive oxygen species. In addition, they can inhibit the migration and invasion of cancer cells. Consistently, Cucurbitacins have been shown to inhibit the Janus kinase-mediated activation of the transcription factor, signal transducer and activator of transcription. In addition, other receptor-mediated signaling pathways, such as ErbB, human epidermal growth factor receptor 2, and integrins, have also been inhibited by the cucurbitacin on cancer cells. Cucurbitacin treatments for various types of cancer have been shown to disrupt the cytoskeletal components such as actin, inhibit the expression of the proto-oncogenic proteins such as c-myc, and induce the expression of tumor suppressor proteins such as p53. Importantly, the synergistic anticancer activities of Cucurbitacins have been observed when combined with established chemotherapeutic drugs, such as imatinib mesylate, paclitaxel, docetaxel, and gemcitabine. Cucurbitacins are a promising anticancer agent and can potentiate the effect of current chemotherapy drugs as well as reduce the serious side effects of these drugs.
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Isolation of anticancer constituents from Cucumis prophetarum var. prophetarum through bioassay-guided fractionation
BMC, 2018Co-Authors: Abdulrhman Alsayari, Lucas Kopel, Mahmoud Salama Ahmed, Hesham S. M. Soliman, Sivakumar Annadurai, Fathi T. HalaweishAbstract:Abstract Background Cucumis prophetarum var. prophetarum is used in Saudi folk medicine for treating liver disorders and grows widely between Abha and Khamis Mushait City, Saudi Arabia. Methods Bioassay-guided fractionation and purification were used to isolate the main active constituents of Cucumis prophetarum var. prophetarum fruits. These compounds were structurally elucidated using NMR spectroscopy, mass spectral analyses and x-ray crystallography. All fractions, sub-fractions and pure compounds were screened for their anticancer activity against six cancer cell lines. Results The greatest cytotoxic activity was found to be in the ethyl acetate fraction, resulting in the isolation of five cucurbitacin compounds [E, B, D, F-25 acetate and Hexanorcucurbitacin D]. Among the Cucurbitacins that were isolated and tested cucurbitacin B and E showed potent cytotoxicity activities against all six human cancer cell lines. Conclusion Human breast cancer cell lines were found to be the most sensitive to Cucurbitacins. Preliminary structure activity relationship (SAR) for cytotoxic activity of Cucurbitacins against human breast cancer cell line MDA-MB-231 has been reported
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mechanistic investigation of hepato protective potential for Cucurbitacins
Medicinal Chemistry Research, 2017Co-Authors: Hajer M Arjaibi, Mahmoud S Ahmed, Fathi T. HalaweishAbstract:Hepatocellular carcinoma is a major example for inflammatory-associated cancer. Cucurbitacins are natural triterpenoids known for their potent anticancer and anti-inflammatory activities. Recent studies showed that Cucurbitacins protect the HepG2 cell lines against carbon tetrachloride-induced toxicity, however the mechanism is unknown. A molecular docking study coupled with in vitro biological assays were conducted to test the hepatoprotective effect of cucurbitacin on the inhibition of potential inflammatory factors. The effect of Cucurbitacins on the activation of NF-kB pathway was analyzed using in cell-based NF-kB immunoassay. Enzyme-linked immunosorbent assays revealed the potential of Cuc D and dihydro cucurbitacin D to prevent the production of tumor necrosis factor-alpha and interleukin-6 from HSC-T6 cells. Thus, Cuc D and dihydro cucurbitacin D could have hepatoprotective effects on the activated rat HSC-T6 cells due to inhibition of the production of tumor necrosis factor-alpha and interleukin-6 through NF-kB pathway. In-silico molecular modeling data revealed potential cucurbitacin analogs with higher binding affinity to the hydrophobic pocket of NF-kB and IKKβ compared to standard IKK inhibitor (PS-1145).
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relationship between Cucurbitacins reversed phase high performance liquid chromatography hydrophobicity index and basal cytotoxicity on hepg2 cells
Journal of Chromatography B, 2005Co-Authors: Judit Bartalis, Fathi T. HalaweishAbstract:Drug development of Cucurbitacins requires derivatives that have lower cytotoxicity. Therefore, the effect of structural modification on in vitro cytotoxicity has been investigated. Lipophilicity or chromatographic hydrophobicity index (CHI) was chosen as molecular property. CHI was determined by RP-HPLC in both aqueous acetonitrile and aqueous methanol. Compounds CHI range was wide and better defined in acetonitrile (CHI(ACN)=46-88 and 38-102) than in methanol (CHI(MeOH)=56-78). Higher resolution was achieved in acetonitrile, and higher precision on the shorter C18 column. Cucurbitacins cytotoxicity (IC(50)) was measured on the hepatocyte-derived HepG2 cells. Strong relationship between CHI and logarithmic IC(50) was found. As a result, cytotoxicity increased linearly with increasing hydrophobicity (r>/=0.90). Other lipophilicity parameters, such as logP and ClogP were also estimated. Cytotoxicity correlated well with logP (r=0.95) and slightly with ClogP (r=0.74). The logP and ClogP data showed good correlation with CHI (r>0.92). Overall, alkylation of C1 hydroxyl, unsaturation of C1C2 bond, and acetylation of C25 hydroxyl increased both lipophilicity and cytotoxicity. This assay should prove useful for monitoring cucurbitacin homologues or other drug candidates for their cytotoxicity.
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Cucurbitacins: A Role in Cucumber Beetle Steroid Nutrition?
Journal of Chemical Ecology, 1999Co-Authors: Fathi T. Halaweish, Douglas W Tallamy, Eva SantanaAbstract:The conditional role of Cucurbitacins as phytosteroid supplements, cholesterol precursors, or ecdysteroid antagonists in the spotted cucumber beetle, Diabrotica undecimpunctata howardi , was investigated in two ways: by comparing larval survival and growth rate on cucurbitacin-rich and cucurbitacin-poor squash cultivars of Cucurbita pepo and by manipulating the presence of cholesterol, phytosteroids, and Cucurbitacins in an artificial diet and examining the effects on adult survival and fecundity. Larvae that developed on cucurbitacin-rich roots grew significantly faster and survived as well as larvae on cucurbitacin-poor roots. There was no evidence, however, that adults could substitute Cucurbitacins in vital phytosteroid roles. Beetles reared on a cucurbitacin-rich, phytosteroid-poor diet laid significantly fewer eggs and died significantly younger than beetles with a full complement of dietary phytosteroids and also laid fewer eggs than beetles with no access to phytosteroids in their adult diet. The data are consistent with the hypothesis that, when the side chain of dietary Cucurbitacins can be successfully hydrogenated, these compounds play a nutritional role as substitutes or precursors for structural steroids. In contrast, when the carbon–carbon double bond cannot be hydrogenated, Cucurbitacins may become antagonists at ecdysteroid receptors, negatively affecting beetle fitness.
Jacques Magdalou - One of the best experts on this subject based on the ideXlab platform.
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the Cucurbitacins e d and i investigation of their cytotoxicity toward human chondrosarcoma sw 1353 cell line and their biotransformation in man liver
Toxicology Letters, 2013Co-Authors: Suzanne Abbas, Pierre Netter, Jean-baptiste Vincourt, Lamice Habib, Helene Greigegerges, Jacques MagdalouAbstract:Cucurbitacins are a class of natural compounds known for their numerous potential pharmacological effects. The purpose of this work was to compare the cytotoxicity of three Cucurbitacins I, D, E on the chondrosarcoma SW 1353 cancer cell line and to investigate their biotransformation in man. Cucurbitacins I and D showed a very strong cytotoxicity, which was higher than that of cytochalasin D, used as a drug reference. Almost 100% of the cells were apoptotic as observed by DNA fragmentation (TUNEL assay) after 12 h with Cucurbitacins I and D (1 μM) and cucurbitacin E (10 μM). In terms of IC(50) values, Cucurbitacins I and E presented a higher toxicity compared to that of cucurbitacin D (MTT assay). Cucurbitacin E was readily hydrolyzed by human hepatic microsomes, leading to cucurbitacin I (K(m) 22 μM, V(max) 571 nmol/mg proteins/min). On the other hand, the three Cucurbitacins were hydroxylated at a very low extent, but they were sulfated and glucuronidated. In terms of V(max)/K(m), the cucurbitacin E was the best substrate of UDP-glucuronosyltransferases. This study shows that Cucurbitacins I, D and E present a potent cytotoxic activity toward the chondrosarcoma SW 1353 cell line and are metabolized as sulfate and glucuronide conjugates.
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the Cucurbitacins e d and i investigation of their cytotoxicity toward human chondrosarcoma sw 1353 cell line and their biotransformation in man liver
Toxicology Letters, 2013Co-Authors: Suzanne Abbas, Pierre Netter, Jean-baptiste Vincourt, Lamice Habib, Helene Greigegerges, Jacques MagdalouAbstract:Abstract Cucurbitacins are a class of natural compounds known for their numerous potential pharmacological effects. The purpose of this work was to compare the cytotoxicity of three Cucurbitacins I, D, E on the chondrosarcoma SW 1353 cancer cell line and to investigate their biotransformation in man. Cucurbitacins I and D showed a very strong cytotoxicity, which was higher than that of cytochalasin D, used as a drug reference. Almost 100% of the cells were apoptotic as observed by DNA fragmentation (TUNEL assay) after 12 h with Cucurbitacins I and D (1 μM) and cucurbitacin E (10 μM). In terms of IC50 values, Cucurbitacins I and E presented a higher toxicity compared to that of cucurbitacin D (MTT assay). Cucurbitacin E was readily hydrolyzed by human hepatic microsomes, leading to cucurbitacin I (Km 22 μM, Vmax 571 nmol/mg proteins/min). On the other hand, the three Cucurbitacins were hydroxylated at a very low extent, but they were sulfated and glucuronidated. In terms of Vmax/Km, the cucurbitacin E was the best substrate of UDP-glucuronosyltransferases. This study shows that Cucurbitacins I, D and E present a potent cytotoxic activity toward the chondrosarcoma SW 1353 cell line and are metabolized as sulfate and glucuronide conjugates.
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The Cucurbitacins E, D and I: Investigation of their cytotoxicity toward human chondrosarcoma SW 1353 cell line and their biotransformation in man liver
Toxicology Letters, 2013Co-Authors: Suzanne Abbas, Pierre Netter, Jean-baptiste Vincourt, Lamice Habib, Hélène Greige-gerges, Jacques MagdalouAbstract:Cucurbitacins are a class of natural compounds known for their numerous ă potential pharmacological effects. The purpose of this work was to ă compare the cytotoxicity of three Cucurbitacins I, D, E on the ă chondrosarcoma SW 1353 cancer cell line and to investigate their ă biotransformation in man. Cucurbitacins I and D showed a very strong ă cytotoxicity, which was higher than that of cytochalasin D, used as a ă drug reference. Almost 100% of the cells were apoptotic as observed by ă DNA fragmentation (TUNEL assay) after 12 h with Cucurbitacins I and D (1 ă mu M) and cucurbitacin E (10 mu M). In terms of IC50 values, ă Cucurbitacins I and E presented a higher toxicity compared to that of ă cucurbitacin D (MTT assay). Cucurbitacin E was readily hydrolyzed by ă human hepatic microsomes, leading to cucurbitacin I (K-m 22 mu M, V-max ă 571 nmol/mg proteins/min). On the other hand, the three Cucurbitacins ă were hydroxylated at a very low extent, but they were sulfated and ă glucuronidated. In terms of V-max/K-m, the cucurbitacin E was the best ă substrate of UDP-glucuronosyltransferases. This study shows that ă Cucurbitacins I, D and E present a potent cytotoxic activity toward the ă chondrosarcoma SW 1353 cell line and are metabolized as sulfate and ă glucuronide conjugates. (C) 2012 Elsevier Ireland Ltd. All rights ă reserved.
Suzanne Abbas - One of the best experts on this subject based on the ideXlab platform.
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the Cucurbitacins e d and i investigation of their cytotoxicity toward human chondrosarcoma sw 1353 cell line and their biotransformation in man liver
Toxicology Letters, 2013Co-Authors: Suzanne Abbas, Pierre Netter, Jean-baptiste Vincourt, Lamice Habib, Helene Greigegerges, Jacques MagdalouAbstract:Cucurbitacins are a class of natural compounds known for their numerous potential pharmacological effects. The purpose of this work was to compare the cytotoxicity of three Cucurbitacins I, D, E on the chondrosarcoma SW 1353 cancer cell line and to investigate their biotransformation in man. Cucurbitacins I and D showed a very strong cytotoxicity, which was higher than that of cytochalasin D, used as a drug reference. Almost 100% of the cells were apoptotic as observed by DNA fragmentation (TUNEL assay) after 12 h with Cucurbitacins I and D (1 μM) and cucurbitacin E (10 μM). In terms of IC(50) values, Cucurbitacins I and E presented a higher toxicity compared to that of cucurbitacin D (MTT assay). Cucurbitacin E was readily hydrolyzed by human hepatic microsomes, leading to cucurbitacin I (K(m) 22 μM, V(max) 571 nmol/mg proteins/min). On the other hand, the three Cucurbitacins were hydroxylated at a very low extent, but they were sulfated and glucuronidated. In terms of V(max)/K(m), the cucurbitacin E was the best substrate of UDP-glucuronosyltransferases. This study shows that Cucurbitacins I, D and E present a potent cytotoxic activity toward the chondrosarcoma SW 1353 cell line and are metabolized as sulfate and glucuronide conjugates.
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the Cucurbitacins e d and i investigation of their cytotoxicity toward human chondrosarcoma sw 1353 cell line and their biotransformation in man liver
Toxicology Letters, 2013Co-Authors: Suzanne Abbas, Pierre Netter, Jean-baptiste Vincourt, Lamice Habib, Helene Greigegerges, Jacques MagdalouAbstract:Abstract Cucurbitacins are a class of natural compounds known for their numerous potential pharmacological effects. The purpose of this work was to compare the cytotoxicity of three Cucurbitacins I, D, E on the chondrosarcoma SW 1353 cancer cell line and to investigate their biotransformation in man. Cucurbitacins I and D showed a very strong cytotoxicity, which was higher than that of cytochalasin D, used as a drug reference. Almost 100% of the cells were apoptotic as observed by DNA fragmentation (TUNEL assay) after 12 h with Cucurbitacins I and D (1 μM) and cucurbitacin E (10 μM). In terms of IC50 values, Cucurbitacins I and E presented a higher toxicity compared to that of cucurbitacin D (MTT assay). Cucurbitacin E was readily hydrolyzed by human hepatic microsomes, leading to cucurbitacin I (Km 22 μM, Vmax 571 nmol/mg proteins/min). On the other hand, the three Cucurbitacins were hydroxylated at a very low extent, but they were sulfated and glucuronidated. In terms of Vmax/Km, the cucurbitacin E was the best substrate of UDP-glucuronosyltransferases. This study shows that Cucurbitacins I, D and E present a potent cytotoxic activity toward the chondrosarcoma SW 1353 cell line and are metabolized as sulfate and glucuronide conjugates.
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The Cucurbitacins E, D and I: Investigation of their cytotoxicity toward human chondrosarcoma SW 1353 cell line and their biotransformation in man liver
Toxicology Letters, 2013Co-Authors: Suzanne Abbas, Pierre Netter, Jean-baptiste Vincourt, Lamice Habib, Hélène Greige-gerges, Jacques MagdalouAbstract:Cucurbitacins are a class of natural compounds known for their numerous ă potential pharmacological effects. The purpose of this work was to ă compare the cytotoxicity of three Cucurbitacins I, D, E on the ă chondrosarcoma SW 1353 cancer cell line and to investigate their ă biotransformation in man. Cucurbitacins I and D showed a very strong ă cytotoxicity, which was higher than that of cytochalasin D, used as a ă drug reference. Almost 100% of the cells were apoptotic as observed by ă DNA fragmentation (TUNEL assay) after 12 h with Cucurbitacins I and D (1 ă mu M) and cucurbitacin E (10 mu M). In terms of IC50 values, ă Cucurbitacins I and E presented a higher toxicity compared to that of ă cucurbitacin D (MTT assay). Cucurbitacin E was readily hydrolyzed by ă human hepatic microsomes, leading to cucurbitacin I (K-m 22 mu M, V-max ă 571 nmol/mg proteins/min). On the other hand, the three Cucurbitacins ă were hydroxylated at a very low extent, but they were sulfated and ă glucuronidated. In terms of V-max/K-m, the cucurbitacin E was the best ă substrate of UDP-glucuronosyltransferases. This study shows that ă Cucurbitacins I, D and E present a potent cytotoxic activity toward the ă chondrosarcoma SW 1353 cell line and are metabolized as sulfate and ă glucuronide conjugates. (C) 2012 Elsevier Ireland Ltd. All rights ă reserved.
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Étude des propriétés de deux séries de substances d'origine naturelle : les cucurbitacines et les parabènes : analyse de leur biotransformation chez l'homme et mesure du pouvoir cytotoxique des cucurbitacines sur une lignée cellulaire de chondrosarco
2012Co-Authors: Suzanne AbbasAbstract:Les cucurbitacines et les parabènes sont des substances d'origine naturelle appartenant à la famille des triterpéniques cycliques et des esters de l'acide-hydroxybenzoïque, respectivement. Ils sont connus pour posséder chez l'homme plusieurs effets pharmacologiques potentiellement intéressants. Le but de ce travail est d'étudier la biotransformation d'une série de trois cucurbitacines et de cinq parabènes dans le foie humain in vitro, essentiellement par glucuronoconjugaison et hydrolyse et caractériser l'effet cytotoxique des cucurbitacines sur une lignée cellulaire du chondrosarcome humain SW 1353. Les résultats ont montré que les cucurbitacines I et D sont plus cytotoxiques que la cytochalasine D vis-à-vis SW 1353 et entraînent l'apoptose des cellules après 12h de traitement à 1 µM alors que la cucurbitacine E présente une cytotoxicité à 10 µM. L'étude in vitro de biotransformation chez l'homme montre que les cucurbitacines sont surtout sulfo- et glucuronoconjuguées (méthodes radiochimiques) par les isoformes de la famille 1A essentiellement. La cucurbitacine E est également activement hydrolysées (Km 22 µM et Vmax 571 nmol/mg /min) en cucurbitacine I dans le foie humain. Par contre, ces substances sont très faiblement hydroxylées. Les acides oléanolique, ursolique et l'érythrodiol, de structure apparentée aux cucurbitacines, sont aussi glucuronoconjuguées au même taux dans les microsomes hépatiques humains mais avec des affinités 100 fois plus élevées. Les parabènes sont rapidement hydrolysés par des estérases dans les microsomes hépatiques humains en acide 4-hydroxybenzoïque, et leur hydrolyse diminue avec la longueur de la chaîne alkyle. Les parabènes, l'acide caféique, le tyrosol et l'hydroxytyrosol, de structure apparentée aux parabènes, sont activement glucuronoconjuguées par les UGTs des familles 1A et 2B. Cependant, l?acide 4-hydroxybenzoïque n'est pas un bon substrat pour les UGTs
Piotr M. Górski - One of the best experts on this subject based on the ideXlab platform.
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Fate of Male-derived Cucurbitacins in Spotted Cucumber Beetle Females
Journal of Chemical Ecology, 2000Co-Authors: Douglas W Tallamy, Piotr M. Górski, Julia K. BurzonAbstract:Using the spotted cucumber beetle, Diabrotica undecimpunctata howardi , as a model species, we begin an examination of the role of dietary Cucurbitacins, the bitter tetracyclic triterpenes produced by cucurbits, in the reproductive behavior of luperine chrysomelids that seek these compounds for purposes other than host-plant recognition or nutrition. By manipulating the cucurbitacin content of adult diets, we determine: (1) how males and females partition Cucurbitacins between reproductive organs and other tissues, (2) the extent to which males pass Cucurbitacins to females during copulation, and (3) if females increase their cucurbitacin stores via multiple matings. After two days of exposure to dietary Cucurbitacins, 8.3 times more Cucurbitacins per gram dry weight were sequestered in male spermatophores than in the aggregate of remaining male tissues. These cucurbitacin-rich spermatophores were passed to females during mating, and 78.8% of the transferred cucurbitacin was deposited in eggs, 11.8% was irreversibly sequestered in other female tissues, and 9.4% was apparently excreted. Females copulated with 0–15 males prior to accepting a complete spermatophere, but did not accept measurable amounts of cucurbitacin from rejected males. Regardless of when it was received, females lost subsequent receptivity to additional males after accepting a complete spermatophore. The implications of these data are discussed in terms of sexual selection hypotheses and mating behavior in cucumber beetles.
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sequestered Cucurbitacins and pathogenicity of metarhizium anisopliae moniliales moniliaceae on spotted cucumber beetle eggs and larvae coleoptera chrysomelidae
Environmental Entomology, 1998Co-Authors: Douglas W Tallamy, Daryl P Whittington, Ferdinand Defurio, David A Fontaine, Piotr M. Górski, Peter W GothroAbstract:It has long been hypothesized that many luperine cucumber beetles ultimately consume and sequester highly bitter cucurbitacin triterpenes to gain protection from predators and possibly parasitoids. Here we expand this protections hypothesis to include antibiotic protection against entontopathogens. Specifically, we examine the ability of Cucurbitacins sequestered in the eggs and larvae of Diabrotica undercimpunctata howardii Barber, the spotted cucumber beetle, to reduce the pathogenicity of the entomopathogen Metarhizium anisopliae, Bitter and nonbitter eggs and larvae (those with and without sequestered cucurbitacin glycosides) were exposed to 0, 10 3 , 10 5 , and 10 7 M. anisopliae conidia per milliliter of distilled water. A significantly greater percentage of both eggs and larvae contining Cucurbitacins survived exposure to the fungus, suggesting that the adaptive value of cucurbitacin pharmacophagy its cucumber beetles includes an antibiotic benefit.
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intra and interspecific genetic variation in the gustatory perception of Cucurbitacins by diabroticite rootworms coleoptera chrysomelidae
Environmental Entomology, 1997Co-Authors: Douglas W Tallamy, Piotr M. Górski, John PesekAbstract:An assay designed to detect the limit of response to the phagostimulant cucurbitacin B was used to quantify intra- and interspecific variation in cucurbitacin perception in adults of the striped cucumber beetle, Acalymma vittatum (F.); the western corn rootworm, Diabrotica virgifera virgifera LeConte; the banded cucumber beetle, D. balteata LeConte; and the spotted cucumber beetle, D. undecimpunctata howardi Barber. By controlling ontogenetic and environmental factors such as gender, age, reproductive status, prior consumption of Cucurbitacins, and hunger, the assay was able to identify geographically based genetic differences in the mean and standard deviation of the limit of response to cucurbitacin B within and among the species tested. Possible sources of this variation and its implications for the use of cucurbitacin-based toxic baits against rootworm pests are discussed.
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Cucurbitacins as feeding and oviposition deterrents to insects
Environmental Entomology, 1997Co-Authors: Douglas W Tallamy, Piotr M. Górski, Jason W Stull, Nathan P Ehresman, Charles E MasonAbstract:Cucurbitacins, the bitter triterpenes common to all Cucurbitaceae, are thought to be potent feeding deterrents for all insects not adapted to exploiting cucurbits. Yet appropriate choice tests not confounded by possible effects from phytochemical induction have only been conducted on a few chrysomelid leaf beetle spp. To examine the extent to which Cucurbitacins deter feeding across several taxa of mandibulate and haustellate insects, we conducted feeding preference tests, pitting host tissues exogenously coated with a methanol dilution of cucurbitacin B against tissues coated with only methanol. Four mandibulate herbivores [ Popillia japonica Newman, Cerotoma trifurcata (Forster), Leptinotarsa decemlineata (Say) and Trichoplusia ni (Hubner)], 2 mandibulate detritivores [ Tenebrio molitor L. and Nauphoeta cinerea (Olivier)] and 4 haustellate herbivores [ Gargaphia solani Heidemann, Corythucha ciliata (Say), Peregrinus maidis (Ashmead), and Acyrthosiphon pisum (Harris)] were examined. We also investigated the ability of cucurbitacin B to deter Ostrinia nubilalis (Hubner) and Spodoptera exiqua (Hubner) females from ovipositing on treated substrates. Two patterns emerged from our feeding assays: nonadapted insects with mandibulate mouthparts were deterred from feeding on food tainted with Cucurbitacins, whereas insects with haustellate mouthparts preferred cucurbitacin-treated food. Oviposition assays with O. nubilalis and S. exiqua revealed significant deterrence at doses of 15 μ g cucurbitacin B per square centimeter. The data suggest that Cucurbitacins are generalized antifeedants for non-adapted mandibulate insects but may actually be phagostimulants for phytophagous insects with haustellate mouthparts. We report on the oviposition deterrence for this class of compounds.