Heteronemin as a Protein Farnesyl Transferase Inhibitor

Ledroit, Veronique; Debitus, Cécile; Ausseil, Frédéric; Raux, Roselyne; Menou, Jean-Louis; Hill, Bridget T.

doi:10.1080/13880200490886120

Cited by 27 publications

(21 citation statements)

References 8 publications

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“…Finally, heteronemin (163) has displayed protein farnesyl transferase inhibition (IC 50 = 3 μM) [120].…”

Section: Pentacyclic Scalaranesmentioning

confidence: 99%

“…[31,32]. 12-Epi-heteronemin (165) was isolated from the sponge Hyrtios erecta collected at New Caledonia [116,120]. 12-Epi-heteronemin acetate (166) was isolated from the sponge Hyrtios erecta collected at the Kingdom of Tonga [28], the sponge Hyrtios sp.…”

Section: Pentacyclic Scalaranesmentioning

confidence: 99%

“…[43], the sponge Lendenfeldia frondosa collected at Solomon Islands [58], and the sponge Phyllospongia dendyi collected at the Indian Ocean [61]. [78], and FXR inhibition [79] 12-O-Deacetyl-scalarin, 86 NGF synthesis-enhancer [81] 12-O-Deacetyl-12-epi-scalarin, 87 Cytotoxic [77], neurotrophic activity [78], and FXR inhibition [79] 25-Dehydroxy-12-epi-scalarin, 90 Antitubercular and cytotoxic [84] 25-Dehydroxy-12-epi-deacetylscalarin, 91 Neurotrophic activity [78], and FXR inhibition [79] 25-Dehydroxy-12-epi-deacetylscalarin, 91 Antitubercular [84,87] and cytotoxic [77,84,86,89] 12-Deacetoxy-19-acetoxyscalarin, 92 Cytotoxic [90] Compounds 96-98 FXR inhibition [79] 12-Deacetoxy-22-hydroxy-25-acetoxyscalarin, 99 Antimicrobial and cytotoxic [37] 12-Deacetoxy-25-acetoxyscalarin, 101 [29,32], ichthyotoxic [34], cytotoxic [31,32,70,84,117,119], antitubercular [31,84,121], and protein farnesyl transferase inhibition [120] Heteronemin acetate, 164 Antimicrobial [32], cytotoxic [31,32,84], and antitubercular [31,84] 12-Epi-heteronemin acetate, 166 Cytotoxic [70]...…”

Section: Miscellaneous Scalaranesmentioning

confidence: 99%

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Scalarane Sesterterpenoids

González

2010

CBC

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“…Finally, heteronemin (163) has displayed protein farnesyl transferase inhibition (IC 50 = 3 μM) [120].…”

Section: Pentacyclic Scalaranesmentioning

confidence: 99%

Section: Pentacyclic Scalaranesmentioning

confidence: 99%

Section: Miscellaneous Scalaranesmentioning

confidence: 99%

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Scalarane Sesterterpenoids

González

2010

CBC

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“…Until now, only two reports on secondary metabolites from H. reticulatus have been published. The first report described 5-hydroxytryptamine-derived alkaloids (β-carbolines) from H. reticulatus collected in south west Sulawesi (Indonesia),7 followed by the sesterterpene heteronemin, isolated by bioassay-guided fractionation with a farnesyl transferase inhibition assay, from H. reticulatus obtained in Vanuatu 8. In this paper, we report the isolation of a new 3-carboxy-β-carboline alkaloid ( 1 ), which we have named hyrtiocarboline, together with the known compounds, sacrotride A ( 2 )9, 10 and 1- O -hexadecyl- sn -glycero-3-phosphocholine ( 3 ),11 from the marine sponge H. reticulatus .…”

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confidence: 99%

A β-Carboline Alkaloid from the Papua New Guinea Marine Sponge Hyrtios reticulatus

et al. 2009

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A new 1-imidazoyl-3-carboxy-6-hydroxy-β-carboline alkaloid, named hyrtiocarboline (1), was isolated from a Papua New Guinea marine sponge Hyrtios reticulatus. The structure was elucidated from spectroscopic data, including 1 H-15 N HMBC NMR experiments that provided complementary 15 N chemical shift information in support of the structure. This compound showed selective anti-proliferative activity against H522-T1 non-small cell lung, MDA-MB-435 melanoma, and U937 lymphoma cancer cell lines.Marine sponges of the genus Hyrtios (Demospongia class, Dictyoceratida order, Thorectidae family) have proven to be a rich and structurally diverse source of cytotoxic compounds as leads for new anticancer therapeutics. The list of cytotoxic compounds spanning several classes of secondary metabolites includes spongistatins1 or altohyrtins2 (macrolides), sesterstatins3 (sesterterpenes), puupehenone4 and 15-oxopuupehenol5 (mixed sesquiterpene-shikimates), and hyrtioerectines6 (tryptamine-derived alkaloids). Until now, only two reports on secondary metabolites from H. reticulatus have been published. The first report described 5-hydroxytryptamine-derived alkaloids (β-carbolines) from H. reticulatus collected in south west Sulawesi (Indonesia), 7 followed by the sesterterpene heteronemin, isolated by bioassay-guided fractionation with a farnesyl transferase inhibition assay, from H. reticulatus obtained in Vanuatu. 8 In this paper, we report the isolation of a new 3-carboxy-β-carboline alkaloid (1), which we have named hyrtiocarboline, together with the known compounds, sacrotride A (2) 9, 10 and 1-O-hexadecyl-sn-glycero-3-phosphocholine (3), 11 from the marine sponge H. reticulatus.The sponge H. reticulatus was collected and preserved according to our standard laboratory procedures, and then stored at 4 °C. 12 The preliminary extraction for bioassay and dereplication analysis was carried out using Accelerated Solvent Extraction (ASE) where approximately 100 g of sponge were extracted with the solvent series hexanes, dichloromethane, and methanol. The dichloromethane and methanol extracts were then tested for antiproliferative activity in a primary screen against U937 histiocytic lymphoma cancer cells, and the dichloromethane extract was found to be active (98.6% inhibition @ 10 μg/mL). four human cancer cell lines, including HT-29 colon cancer cells (3.8 μg/mL), H522-T1 nonsmall-cell cancer cells (8.0 μg/mL), MDA-MB-435 melanoma (0.9 μg/mL), and U937 histiocytic lymphoma cells (2.9 μg/mL). Dereplication analysis of the extract was conducted using a HPLC-UV-ELSD-MS system equipped with a C 18 HPLC column, and a binary mobile phase of acetonitrile/0.1% formic acid and water/0.1% formic acid, spanning a gradient from 10% to 100% acetonitrile over 30 min. The resulting UV-DAD and MS data for the major peaks were then cross-checked for reported structures in MarinLit. 14 Three peaks with molecular ions at m/z 323, 463 and 482 did not correspond to any reported compounds based on mass and occurrence in Hyrtios and were designat...

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“…This natural marine compound was found to inhibit the enzyme protein farnesyltransferase and reduce the viability of leukemia cells, colon cancer cells, and breast cancer cells. 11,12 The potential inflammation inhibitory and apoptosis-inducing effects of HET on leukemia cells in vitro have also been reported. 13 However, before the conduction of in vivo animal trials, further investigation into the antitumor effects of HET against other tumor cells is required to clarify the effective extension and strength as well as the mechanisms of apoptotic induction by HET.…”

Section: Introductionmentioning

confidence: 99%

Improvement and enhancement of antibladder carcinoma cell effects of heteronemin by the nanosized hyaluronan aggregation

Huang

Kuo

et al. 2016

IJN

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The effects against tumors exerted by marine active compounds have been highlighted and investigated. Polymeric nanoparticles made from biodegradable and biocompatible molecules such as hyaluronan (HA) and chitosan (CHI) are able to aggregate the compounds to enhance their activities against tumor cells and reduce the toxicity on normal cells. Here, we extensively examined the antitumor activities and the mechanisms of HA/CHI nanoparticles-aggregated heteronemin (HET) extracted from the sponge Hippospongia sp. The half-maximal inhibitory concentration (IC 50 ) of pure HET toward T24 bladder carcinoma cells is ~0.28 µg/mL. Pure HET from 0.2 to 0.8 µg/mL and HA nanoparticles-aggregated HET at 0.1 and 0.2 µg/mL significantly reduced T24 cell viability. Compared to pure HET, HA nanoparticles/HET aggregates showed much weaker viability-inhibitory effects on L929 normal fibroblasts. HET dose-dependently suppressed cancer cell migration as HA/CHI nanoparticles-aggregated HET displayed stronger migration-inhibitory effects than pure HET. Flow cytometric analysis showed that pure HET increased early/total apoptosis and JC-1 monomer fluorescence, while HA/CHI nanoparticles-aggregated HET induced higher apoptosis and JC-1 monomer rates than pure HET, suggesting that aggregation of HA nanoparticles offers HET stronger apoptosis-inducing capacity through mitochondrial depolarization. Western blot analysis showed that HA nanoparticles-aggregated HET further increased mitochondrial-associated, caspase-dependent and caspase-independent, as well as endoplasmic reticulum stress-related factors in comparison with pure HET. These data indicated that pure HET possesses cytotoxic, antimigratory, and apoptosis-inducing effects on bladder cancer cells in vitro, and its induction of apoptosis in bladder carcinoma cells is mainly caspase dependent. Moreover, HA nanoparticle aggregation reinforced the cytotoxic, antimigratory, and apoptosis-inducing activities against bladder carcinoma cells and attenuated the viability-inhibitory effects on normal fibroblasts. This aggregation reinforces antibladder carcinoma effects of HET via diverse routes, including mitochondrial-related/caspase-dependent, caspase-independent, and endoplasmic reticulum stress-related pathways. The current data also strongly suggested that HA/CHI nanoparticles-aggregated HET would be a potential treatment for urothelial cancer in vivo.

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Heteronemin as a Protein Farnesyl Transferase Inhibitor

Cited by 27 publications

References 8 publications

Scalarane Sesterterpenoids

Scalarane Sesterterpenoids

A β-Carboline Alkaloid from the Papua New Guinea Marine Sponge Hyrtios reticulatus

Improvement and enhancement of antibladder carcinoma cell effects of heteronemin by the nanosized hyaluronan aggregation

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