ChemInform Abstract: Girolline, a New Antitumoral Compound Extracted from the Sponge, Pseudaxinyssa cantharella n. sp. (Axinellidae)

Ahond, A.; Zurita, M. Bedoya; Colin, Margaux; Fizames, C.; Laboute, Pierre; Lavelle, François; Désiré, Laurent; Poupat, C.; Pusset, J.; Pusset, M.; Thoison, Odile; Potìer, Pierre

doi:10.1002/chin.198844342

Cited by 26 publications

(38 citation statements)

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“…Among all marine organisms, sponges represent one of the most promising source of marine bioactive compounds particularly for pharmaceutical leads [5,6]. In order to purify new active compounds with biological activities and potential application in biomedicine, extracts from marine sponges around the world have been examined for antineoplastic activity in various tumor cell lines, as well as in animal models [7][8][9][10][11][12][13][14]. At least two drugs (Ara-A and Ara-C) synthetically derived from sponge metabolites have been clinically used in long-term cancer treatments [15].…”

Section: Introductionmentioning

confidence: 99%

Brazilian marine sponge Polymastia janeirensis induces apoptotic cell death in human U138MG glioma cell line, but not in a normal cell culture

et al. 2008

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Marine sponges have been prominently featured in the area of cancer research. Here, we examined the anti-proliferative effects of crude extracts (aqueous and organic) of the Brazilian marine sponge Polymastia janeirensis in the U138MG human glioma cell line. Moreover, we examined the effects of extracts on selective cytotoxicity in the glioma cells in comparison with a normal cell culture. Exposure of glioma cells to treatments (24 h) resulted in cell number decrease at all doses tested, with both aqueous and organic extracts (IC(50) <20 and <30 microg/ml, respectively). Parallel to this result, sponge extracts reduced glioma cell viability (IC(50) <15 microg/ml for both extracts). However, higher doses (50 and 100 microg/ml) induced a stronger cytotoxic effect when compared to the lower dose tested (10 microg/ml), inhibiting more than 80% of cellular growth and viability. Propidium iodide uptake and flow cytometry analysis further showed that sponge extracts caused necrosis in the glioma cell line at higher doses, while a high percentage of apoptotic glioma cells were observed at 10 microg/ml. Moreover, apoptosis was prevented by the pan-caspase inhibitor Z-VAD, suggesting that marine sponge extracts, at lower doses, induce caspase-dependent apoptosis in U138MG glioma cells. Surprisingly the extracts herein tested were more effective than temozolomide, a potent inductor of apoptosis used for the treatment of malignant gliomas. Furthermore, our results suggested a selectivity cytotoxic effect on glioma cell line in comparison with a normal cell culture, since the effect on viability found in glioma cells was not observed in astrocyte cultures with the lower dose (10 microg/ml). Thus, this marine sponge may be considered a good candidate for development of new cancer medicines with antitumor activity against gliomas.

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Section: Introductionmentioning

confidence: 99%

Brazilian marine sponge Polymastia janeirensis induces apoptotic cell death in human U138MG glioma cell line, but not in a normal cell culture

et al. 2008

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“…8) was originally isolated as an antitumor compound from the marine sponge, Peudaxinyssa cantharella, collected in New Caledonia [32]. This compound exhibits significant cytotoxicity in vitro against several tumor cell lines and in vivo against murine grafted tumors and solid tumors.…”

Section: Inhibitor Of P53-hdm2 Interactionmentioning

confidence: 99%

The search for inhibitors of the ubiquitin–proteasome system from natural resources for drug development

Tsukamoto

2006

J Nat Med

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The ubiquitin-proteasome proteolytic pathway plays a major role in selective protein degradation and regulates various cellular events, including cell cycle progression, transcription, DNA repair, signal transduction, and immune response. In this pathway, ubiquitin, a highly conserved small protein in eukaryotes, attaches to a target protein prior to degradation. The polyubiquitin chains are recognized by the 26S proteasome, and the protein portion is degraded by the proteolytic active sites in a cavity in the 26S proteasome. The potential of specific proteasome inhibitors, which act as anti-cancer agents, is now under intensive investigation, and bortezomib (PS-341, Velcade), a proteasome inhibitor, was approved by the FDA for multiple myeloma treatment in 2003. Since ubiquitination of proteins requires the sequential action of three enzymes-ubiquitin-activating enzyme (E1), ubiquitin-conjugating enzyme (E2), and ubiquitinprotein ligase (E3)-and polyubiquitination is a prerequisite for proteasome-mediated protein degradation, inhibitors of E1, E2, and E3 are reasonably thought to be drug candidates for treatment of diseases related to ubiquitination. In the course of our search for new classes of inhibitors against the ubiquitin-proteasome proteolytic pathway from natural resources for drug development, we succeeded in isolating agosterols, secomycalolides A, and 1,3-diphenylpropane derivatives as inhibitors of chymotrypsin-like activity of the proteasome, himeic acid A as an E1 inhibitor, and (-)-hexylitaconic acid as an inhibitor of p53-HDM2interaction. In addition, we found that girolline, an anticancer compound, is the first agent inhibiting the recruitment of polyubiquitinated p53 to the proteasome.

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“…In order to identify new active compounds with antitumor activity, extracts from a number of species of marine sponges have been examined in various tumor cell lines, as well as in animal models [4][5][6][7][8][9][10][11]. At least two drugs (Ara-A and Ara-C) synthetically derived from sponge metabolites have been clinically used in long-term cancer treatments [12].…”

Section: Introductionmentioning

confidence: 99%

Extracts of marine sponge Polymastia janeirensis induce oxidative cell death through a caspase-9 apoptotic pathway in human U138MG glioma cell line

Frota¹,

Braganhol²,

Cañedo³

et al. 2008

Invest New Drugs

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We have studied the apoptotic pathway activated in response to marine sponge extracts of Polymastia janeirensis. The effect on intracellular ROS production was also examined. Exposure of U138MG glioma cell line to doses higher than 5 microg/mL has decreased glioma cell viability, with an IC(50) <15 microg/mL for both aqueous and organic extracts. However, extracts at higher doses (50 and 100 microg/mL) have stronger cytotoxic effects, decreasing more than 90% of glioma cell viability. The antioxidant Trolox (100 microM) reversed the cell death percentage induced by extracts at 10 and 25 microg/mL. The type of cell death induced by such high doses was predominantly necrosis, while a high percentage of apoptotic glioma cells was found at 10 microg/mL. Moreover, inhibition of caspase-8 with Z-IETD (a caspase-8 inhibitor) had no effect on the amount of apoptosis induced by 10 microg/mL, but inhibition of caspase-9 with Z-LEHD (a caspase-9 inhibitor) decreased apoptosis. We also observed a dose-dependent increase in ROS production, and similarly to effects observed on viability of glioma cells, and on cell death, higher doses also had more severe effects. Co-treatment with Trolox significantly reduced ROS production by extracts at doses lower than 50 microg/mL. This is a first report demonstrating that marine sponge extracts of P. janeirensis induce oxidative cell death through a caspase-9 apoptotic pathway.

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ChemInform Abstract: Girolline, a New Antitumoral Compound Extracted from the Sponge, Pseudaxinyssa cantharella n. sp. (Axinellidae)

Abstract: ChemInform Abstract (active on P 388 leukemia in vivo and in vitro).

Cited by 26 publications

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Brazilian marine sponge Polymastia janeirensis induces apoptotic cell death in human U138MG glioma cell line, but not in a normal cell culture

Brazilian marine sponge Polymastia janeirensis induces apoptotic cell death in human U138MG glioma cell line, but not in a normal cell culture

The search for inhibitors of the ubiquitin–proteasome system from natural resources for drug development

Extracts of marine sponge Polymastia janeirensis induce oxidative cell death through a caspase-9 apoptotic pathway in human U138MG glioma cell line

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