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At least 199 records · Page 11Linked to original sources
PubMed2006

Identification of norharman as the cytotoxic compound produced by the sponge (Hymeniacidon perleve)-associated marine bacterium Pseudoalteromonas piscicida and its apoptotic effect on cancer cells.

Marine invertebrates harbour a wealth of micro-organisms in their bodies. Most of these micro-organisms can catabolize antibiotic compounds as chemical-defence compounds. These compounds not only play an important protective role for their producer and for their hosts, but also have high potential in medicinal applications. In order to discover natural anticancer products, 29 marine bacterial strains have been isolated from the sponge Hymeniacidon perleve, samples of which were collected from the intertidal zone during low tide off Nanji island in Eastern China. By means of a cytotoxicity bioassay, one strain, NJ6-3-1, with significant cytotoxic activity, was selected for culture in a 30-litre fermentation tank. The major cytotoxic compound in the metabolites of NJ6-3-1, separated by means of a bioassay-guided fractionation process, has been identified as norharman (a beta-carboline alkaloid) by electron-impact MS and NMR analyses. Norharman showed cytotoxicity towards both the HeLa cervical-cancer cell line and the BGC-823 stomach-cancer cell line, with an IC(50) of 5 microg/ml. Several methods were used to study the mechanism by which norharman is cytotoxic to HeLa cells. By means of an Acridine Orange/ethidium bromide dual-staining assay, condensation of chromatin was observed. A TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling) assay showed degradation of DNA. Flow-cytometric analysis indicated that norharman could arrest cells at the G(2)/M phase of the cell cycle. These results demonstrate the cytotoxic mechanism of norharman involves the induction of apoptosis in HeLa cells.

Animals↗
PubMed2003

An antitumour lectin from the edible mushroom Agrocybe aegerita.

An antitumour lectin (named AAL) consisting of two identical subunits of 15.8 kDa was isolated from the fruiting bodies of the edible mushroom Agrocybe aegerita using a procedure which involved precipitating the extract by addition of (NH(4))(2)SO(4), ion exchange chromatography on DEAE-Sepharose Fast Flow, gel filtration chromatography on Sephacryl S-200 HR and finally purification on a GF-250 HPLC column. Amino acid analysis of the N-terminus and an internal fragment indicated that the sequences of the two fragments were QGVNIYNI and Q(K)PDGPWLVEK(Q)R respectively. AAL showed strong inhibition of the growth of human tumour cell lines HeLa, SW480, SGC-7901, MGC80-3, BGC-823, HL-60 and mouse sarcoma S-180. AAL also inhibited the viability of S-180 tumour cells in vivo. Analysis by Hoechst 33258 staining, MitoSensor Kit and flow cytometry showed that AAL induced apoptosis in HeLa cells. TUNEL (terminal transferase deoxytidyl uridine end labelling) analysis of slides of tumour tissues excised from BALB/c mice also demonstrated the apoptosis-induction activity of the lectin. Furthermore, AAL was shown to possess DNase activity in assays using plasmid pCDNA3 and salmon sperm DNA. Based on the results obtained in these assays, we conclude that AAL exerts its antitumour effects via apoptosis-inducing and DNase activities.

Agaricales↗
PubMed2002

New macrocyclic diterpenoids from Euphorbia esula.

The structures of two new macrocyclic jatrophane diterpenoid esters from the whole herb of Euphorbia esula, were established as 11,14-epoxy-3beta,5alpha,7beta,8alpha,9alpha,15beta-hexaacetoxy-12-oxo-13alphaH-jatropha-6(17)-ene (1) and 1alpha,3beta-diacetoxy-5alpha,7beta-dibenzoyloxy-9,14-dioxo-11beta,12alpha-epoxy-2alpha,8alpha,15beta-trihydroxy-13betaH-jatropha-6(17)-ene (2) by a combination of 1D- and 2D-NMR techniques as well as UV, IR and mass spectral data. Bioassay evaluation of all isolates against the human tumor cell lines (B16, KB, SMMC and BGC) indicated that ester 2 was cytotoxic to B16 with the IC50 value being 1.81 microg/ml. In addition, the irritant activity assay indicated that both diterpenoids were inactive (ID(24)50 > 100 microg/ear).

Animals↗
PubMed2003

Induction of apoptosis and G2/M cell cycle arrest by Gleditsioside E from Gleditsia sinensis in HL-60 cells.

Gleditsioside E, a triterpene saponin isolated from Gleditsia sinensis, showed significant cytotoxicity against Bel-7402, BGC-823, HeLa, HL-60 and MCF-7 cell lines. The results of flow cytometry with annexin V-FITC/PI double staining proved that gleditsioside E mainly induced early apoptosis in HL-60 cells. Gleditsioside E treatment resulted in a prominent increase of the G 2 /M population in HL-60 cells, and an accumulation of the sub-G 1 (hypoploid) peak was observed.

Antineoplastic Agents, Phytogenic↗
PubMed2004

Effects of albaconol from the basidiomycete Albatrellus confluens on DNA topoisomerase II-mediated DNA cleavage and relaxation.

The effect of albaconol on the growth of human tumor cell, DNA topoisomerase (topo)-mediated DNA cleavage and direct DNA breakage was investigated. Albaconol inhibited significantly the growth of the human tumor cell lines K562, A549, BGC-823 and Bcap-37, the IC5s values were 7.99 +/- 0.4, 3.17 +/- 0.89, 4.18 +/- 0.14 and 7.45 +/- 2.5 microM, respectively. Albaconol stabilized and increased the topo 11-mediated DNA cleavable complex and inhibited the religation activity of topo II in a dose-dependent manner, but it failed to affect the activity of topo I. Albaconol directly broke pBR322 DNA at high concentrations, but there was no effect on the macromolecule of K562 cells. These results strongly suggest that albaconol targeted specifically to DNA topo II and that this is one of the mechanisms of its antitumor action; the direct action of albaconol on DNA may partly contribute to its anti-tumor activity at high concentrations.

Antineoplastic Agents, Phytogenic↗
PubMed2005

Cytotoxic and antifungal isoprenylated xanthones and flavonoids from Cudrania fruticosa.

A new isoprenylated xanthone, cudrafrutixanthone A, was isolated from the roots of Cudrania fruticosa, together with 18 known compounds. Their structures were elucidated by spectroscopic methods. Most isoprenylated xanthones exhibited cytotoxicity against HCT-116, SMMC-7721, SGC-7901, and BGC-823 cell lines with IC (50) values of 1 - 5 microg/mL. Toxyloxanthone C and wighteone showed antifungal activity against Candida albicans with MICs of 25 and 12.5 microg/mL, respectively.

Antifungal Agents↗
PubMed2006

New triterpenoids from Kadsura heteroclita and their cytotoxic activity.

Phytochemical investigations of the stem of Kadsura heteroclita (Roxb) Craib (Schizandraceae) resulted in the isolation and structure elucidation of six new triterpenoidal compounds named heteroclitalactones A-E (1-5) as well as heteroclic acid (6) and heteroclitalactone F (7), which was isolated for the first time from a natural source, and the six known compounds schisanlactone E (8), cycloartenone (9), schisandronic acid (10), nigranoic acid (11), changnanic acid (12) and schisanlactone B (13), respectively. The structures of these compounds were characterized by extensive 1D and 2D NMR spectral analyses. The majority of these triterpenoids showed moderate cytotoxic activity against the human tumor cell lines Bel-7402, BGC-823, MCF-7 and HL-60. Among the compounds tested, heteroclitalactone D (4) showed the strongest cytotoxic activity against the HL-60 cells with an IC50 of 6.76 microM.

Antineoplastic Agents, Phytogenic↗
PubMed2006

New cassaine diterpenoid amides with cytotoxic activities from the bark of Erythrophleum fordii.

A phytochemical investigation of the bark of Erythrophleum fordii led to six new cassaine diterpenoid amides (2, 4-8), together with two known compounds of the same skeleton, nor-cassamide ( 1) and nor-erythrosuamide (3). The structures were mainly established on the basis of 1D, 2D NMR and HR-MS analysis. The compounds 1, 2, 4, 6-8 exhibited selective cytotoxic activities (IC50 values < 10 microM) against A2780, KB, Bel-7402, BGC-823, MCF-7, HCT-8, Hela, PC-3M, A549 and Ketr3 human cancer cell lines in the MTT test.

Abietanes↗
PubMed2003

Juvenile sarcoidosis after BCG vaccination.

We report the case of a 2-year-old boy with juvenile sarcoidosis, in whom the cutaneous lesions first arose at the site of and soon after a BCG vaccination. Juvenile sarcoidosis is rare, and the pattern of clinical features is distinct from the adult form of sarcoidosis, possibly related to immunologic development. The cause of sarcoidosis is unknown, although there is much interest in the possibility of mycobacterial species operating as antigenic stimuli to initiate the disease. This case suggests that the Mycobacterium bovis present in the BGC vaccination may have been etiologically important in the development of sarcoidosis.

Antigens, Bacterial↗
PubMed2001

A new sesquiterpene lactone from Tsoongiodendron odorum Chun.

A new sesquiterpene lactone (1) was obtained from the cytotoxic fraction of 95% ethanol extract of root barks of Tsoongiodendron odorum Chun together with two known sesquiterpene lactones, costunolide (2) and parthenolide (3). The structure of 1 was elucidated as 5alpha, 6alpha, 7beta, 10beta- 11alpha, 13-dihydro-4(15)-eudesmene-12, 6-olide on the basis of chemical and spectral evidence including X-ray diffraction analysis. Costunolide showed cytotoxic activity against human leukemia (HL-60) cell line. Parthenolide showed promising cytotoxic activities in vitro against HCT-8, Bel-7402, SKOV3, KB, HELA and EJ cell lines. Also, the cytotoxic ethyl acetate fraction of ethanol extract of the root barks from which three chemical components were isolated showed promising cytotoxic activities in vitro against KB, BGC-823, Bel-7402, HCT-8, HL-60 cell lines.

Antineoplastic Agents, Phytogenic↗
PubMed2003

Bioactive triterpenoids from Symplocos chinensis.

A new triterpenoid, 2beta,3beta,19alpha,24-tetrahydroxy-23-norurs-12-en-28-oic acid (4), together with three known triterpenoids 3-oxo-19alpha,23,24-trihydroxyurs-12-en-28-oic acid (1), 2alpha,3beta,19alpha,23-tetrahydroxyurs-12-en-28-oic acid (2), 2alpha,3alpha,19alpha,23-tetrahydroxyurs-12-en-28-oic acid (3), was isolated from the roots of Symplocos chinensis. The new triterpenoid shows significant cytotoxic activity against B16 and BGC-823 cells.

Antineoplastic Agents↗
PubMed2005

Microbial hydroxylation of cinobufagin by Mucor spinosus.

Mucor spinosus has been employed for the biotransformation of cinobufagin (1) to afford three metabolites. On the basis of their physico-chemical data, the structures of the transformation products have been characterized as 1beta-hydroxy-cinobufagin (2), 12beta-hydroxy-cinobufagin (3) and 1beta,12beta-dihydroxy-cinobufagin (4), of which metabolites 2 and 4 are new compounds. In vitro cytotoxic activities of the biotransformation products and the substrate-cinobufagin have been assayed against four tumor cell lines of Bel 7420, BGC 823, HeLa and HL 60; they all showed cytotoxic activities.

Biotransformation↗
PubMedDate not supplied

Julibroside J8-induced HeLa cell apoptosis through caspase pathway.

The julibroside J8 was isolated from the Albizia julibrissin and evaluated for antiproliferatived on six cancer cell lines (BGC-823, Bel-7402, HeLa, PC-3MIE8, MDA-MB-435 and LH-60) in vitro. Julibroside J8 at 100 microg mL- 1 (46.08 micromol.L- 1) significantly inhibited growth in the first three cell lines. In addition, in HeLa cells typical apoptotic changes in morphology were observed, and further, nuclear damage was observed by Giemsa staining and DNA fragmentation was exhibited. Effects of julibrosideJ8 on induction of DNA fragmentation, caspase-3 activation and downregulation of ICAD expression were effectively inhibited by a caspase-3 inhibitor, z-DEVD-fmk. In addition, apoptosis induced with julibroside J8 was associated with an increase in expression of the apoptosis inducer Bax, and a significant reduction in expression of the apoptosis suppressor Bcl-2 in mitochondria. These results suggest that julibroside J8 induces HeLa death through caspase pathway.

Albizzia↗
PubMed2025

CAGEcleaner: reducing genomic redundancy in gene cluster mining.

SUMMARY: Mining homologous biosynthetic gene clusters (BGCs) typically involves searching colocalised genes against large genomic databases. However, the high degree of genomic redundancy in these databases often propagates into the resulting hit sets, complicating downstream analyses and visualization. To address this challenge, we present CAGEcleaner, a Python-based pipeline with auxiliary bash scripts designed to reduce redundancy in gene cluster hit sets by dereplicating the genomes that host these hits. CAGEcleaner integrates seamlessly with widely used gene cluster mining tools, such as cblaster and CAGECAT, enabling efficient filtering and streamlining BGC discovery workflows. AVAILABILITY AND IMPLEMENTATION: Source code and documentation is hosted at GitHub (https://github.com/LucoDevro/CAGEcleaner) and Zenodo (https://doi.org/10.5281/zenodo.14726119) under an MIT license. For accessibility, CAGEcleaner is installable from Bioconda (https://anaconda.org/bioconda/cagecleaner) and PyPi (https://pypi.org/project/cagecleaner/), and is also available as a Docker image from DockerHub (https://hub.docker.com/r/lucodevro/cagecleaner).

Software↗
PubMed2026

Nerpa 2: probabilistic linking of biosynthetic gene clusters to nonribosomal peptides.

MOTIVATION: Nonribosomal peptides (NRPs) are bioactive microbial metabolites with high pharmaceutical potential. Although genome mining enables large-scale detection of biosynthetic gene clusters (BGCs) predicted to encode NRPs, reliably linking these clusters to their chemical products remains challenging due to the flexible and heterogeneous organization of NRP assembly pathways. RESULTS: We present Nerpa 2, a probabilistic framework for accurate and scalable linking of NRP BGCs to candidate chemical structures. The method represents assembly lines as hidden Markov models (HMMs) that capture uncertainty and alternative biosynthetic routes. On curated datasets of experimentally validated BGC-product pairs, our tool outperforms existing methods in linking accuracy and pathway reconstruction. When applied to large genome mining datasets, Nerpa 2 efficiently identifies BGCs likely associated with known compounds and highlights potential producers of novel chemistry. AVAILABILITY AND IMPLEMENTATION: Nerpa 2 is freely available at https://github.com/gurevichlab/nerpa.

Multigene Family↗
PubMedDate not supplied

Simulating forest productivity and surface-atmosphere carbon exchange in the BOREAS study region.

A process-based, general ecosystem model (BIOME-BGC) was used to simulate daily gross primary production, maintenance and heterotrophic respiration, net primary production and net ecosystem carbon exchange of boreal aspen, jack pine and black spruce stands. Model simulations of daily net carbon exchange of the ecosystem (NEE) explained 51.7% (SE = 1.32 g C m(-2) day(-1)) of the variance in daily NEE derived from stand eddy flux measurements of CO(2) during 1994. Differences between measured and simulated results were attributed to several factors including difficulties associated with measuring nighttime CO(2) fluxes and model assumptions of site homogeneity. However, comparisons between simulations and field data improved markedly at coarser time-scales. Model simulations explained 66.1% (SE = 0.97 g C m(-2) day(-1)) of the variance in measured NEE when 5-day means of daily results were compared. Annual simulations of aboveground net primary production ranged from 0.6-2.4 Mg C ha(-1) year(-1) and were concurrent with results derived from tree increment core measurements and allometric equations. Model simulations showed that all of the sites were net sinks (0.1-4.1 Mg C ha(-1) year(-1)) of atmospheric carbon for 1994. Older conifer stands showed narrow margins between uptake of carbon by net photosynthesis and carbon release through respiration. Younger stands were more productive than older stands, primarily because of lower maintenance respiration costs. However, all sites appeared to be less productive than temperate forests. Productivity simulations were strongly linked to stand morphology and site conditions. Old jack pine and aspen stands showed decreased productivity in response to simulated low soil water contents near the end of the 1994 growing season. Compared with the aspen stand, the jack pine stand appeared better adapted to conserve soil water through lower daily evapotranspiration losses but also exhibited a narrower margin between daily net photosynthesis and respiration. Stands subjected to water stress during the growing season may exist on the edge between being annual sources or sinks for atmospheric carbon.

Journal Article↗
PubMed2000

Regional assessment of boreal forest productivity using an ecological process model and remote sensing parameter maps.

An ecological process model (BIOME-BGC) was used to assess boreal forest regional net primary production (NPP) and response to short-term, year-to-year weather fluctuations based on spatially explicit, land cover and biomass maps derived by radar remote sensing, as well as soil, terrain and daily weather information. Simulations were conducted at a 30-m spatial resolution, over a 1205 km(2) portion of the BOREAS Southern Study Area of central Saskatchewan, Canada, over a 3-year period (1994-1996). Simulations of NPP for the study region were spatially and temporally complex, averaging 2.2 (+/- 0.6), 1.8 (+/- 0.5) and 1.7 (+/- 0.5) Mg C ha(-1) year(-1) for 1994, 1995 and 1996, respectively. Spatial variability of NPP was strongly controlled by the amount of aboveground biomass, particularly photosynthetic leaf area, whereas biophysical differences between broadleaf deciduous and evergreen coniferous vegetation were of secondary importance. Simulations of NPP were strongly sensitive to year-to-year variations in seasonal weather patterns, which influenced the timing of spring thaw and deciduous bud-burst. Reductions in annual NPP of approximately 17 and 22% for 1995 and 1996, respectively, were attributed to 3- and 5-week delays in spring thaw relative to 1994. Boreal forest stands with greater proportions of deciduous vegetation were more sensitive to the timing of spring thaw than evergreen coniferous stands. Similar relationships were found by comparing simulated snow depth records with 10-year records of aboveground NPP measurements obtained from biomass harvest plots within the BOREAS region. These results highlight the importance of sub-grid scale land cover complexity in controlling boreal forest regional productivity, the dynamic response of the biome to short-term interannual climate variations, and the potential implications of climate change and other large-scale disturbances.

Journal Article↗
PubMed2003

Modeling effects of hydrological changes on the carbon and nitrogen balance of oak in floodplains.

We extended the applicability of the ecosystem model BIOME-BGC to floodplain ecosystems to study effects of hydrological changes on Quercus robur L. stands. The extended model assesses floodplain peculiarities, i.e., seasonal flooding and water infiltration from the groundwater table. Our interest was the tradeoff between (a). maintaining regional applicability with respect to available model input information, (b). incorporating the necessary mechanistic detail and (c). keeping the computational effort at an acceptable level. An evaluation based on observed transpiration, timber volume, soil carbon and soil nitrogen content showed that the extended model produced unbiased results. We also investigated the impact of hydrological changes on our oak stands as a result of the completion of an artificial canal network in 1971, which has stopped regular springtime flooding. A comparison of the 11 years before versus the 11 years after 1971 demonstrated that the hydrological changes affected mainly the annual variation across years in leaf area index (LAI) and soil carbon and nitrogen sequestration, leading to stagnation of carbon and nitrogen stocks, but to an increase in the variance across years. However, carbon sequestration to timber was unaffected and exhibited no significant change in cross-year variation. Finally, we investigated how drawdown of the water table, a general problem in the region, affects modeled ecosystem behavior. We found a further amplification of cross-year LAI fluctuations, but the variance in soil carbon and nitrogen stocks decreased. Volume increment was unaffected, suggesting a stabilization of the ecosystem two decades after implementation of water management measures.

Carbon↗