Browse
Submit Data
Databases
API
Help

Dataset Information

10 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Screening of Promising Chemotherapeutic Candidates from Plants against Human Adult T-Cell Leukemia/Lymphoma (VII): Active Principles from Thuja occidentalis L.

ABSTRACT: During the screening of novel chemotherapeutic candidates from plants against adult T-cell leukemia/lymphoma, we identified that the extracts of Thuja occidentalis (Cupressaceae) showed potent anti-proliferative activity in MT-1 and MT-2 cells. Therefore, we attempted to isolate the active components from this plant. We isolated and identified 32 compounds (1-32; eight lignans, 18 terpenoids, and six flavonoids) from the extracts of the leaves and cones. Their structures were determined by spectroscopic analysis. Several of the isolated compounds inhibited the growth of both cell lines. Lignans showed more potent activity than other classes of compounds. A comparison of the activities of compounds 1-8 revealed that the presence of a trans-lactone (linkage of C-6 to C-7) correlated with increased activity. Diterpenes showed moderate activity, and the presence of a ketone moiety at the C-7 position correlated with increased activity in compounds 12-21. In addition, biflavones showed moderate activity, and the presence of methoxy functions appeared to influence the activity of these compounds. Several lignans were lead compound of anti-cancer reagent (etoposide). In conclusion, not only lignans, but also diterpenes and/or biflavones, may be promising candidates for the treatment of adult T-cell leukemia/lymphoma.

SUBMITTER: Nakano D

PROVIDER: S-EPMC8707666 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Development and multiplexed amplification of SSR markers for Thuja occidentalis (Cupressaceae) using shotgun pyrosequencing.

Project description:Sixteen novel, polymorphic, multiplexed microsatellite loci were developed for eastern white cedar (Thuja occidentalis) using simple sequence repeat (SSR)-enriched shotgun pyrosequencing. • Sixteen loci were tested on a panel of 24 individuals from different populations. The number of observed alleles ranged from four to 22. Four sets of multiplex PCR for the 16 loci were then carried out on 60 individuals of two populations from islands of FERLD Duparquet Forest, Canada. Mean number of alleles, observed heterozygosity, and expected heterozygosity were respectively 5.75, 0.594, and 0.574 for Island 58, and 5.50, 0.704, and 0.624 for Island 134. • Four sets of multiplex microsatellite loci can be used for future genetic studies, which includes investigating genetic diversity and structure, and fragmentation and regeneration studies.

| S-EPMC4105039 | biostudies-literature

Rapid response to anthropogenic climate change by <i>Thuja occidentalis</i>: implications for past climate reconstructions and future climate predictions.

Project description:Carbon isotope values of leaves (δ13Cleaf) from meta-analyses and growth chamber studies of C3 plants have been used to propose generalized relationships between δ13Cleaf and climate variables such as mean annual precipitation (MAP), atmospheric concentration of carbon dioxide ([CO2]), and other climate variables. These generalized relationships are frequently applied to the fossil record to create paleoclimate reconstructions. Although plant evolution influences biochemistry and response to environmental stress, few studies have assessed species-specific carbon assimilation as it relates to climate outside of a laboratory. We measured δ13Cleaf values and C:N ratios of a wide-ranging evergreen conifer with a long fossil record, Thuja occidentalis (Cupressaceae) collected 1804-2017, in order to maximize potential paleo-applications of our focal species. This high-resolution record represents a natural experiment from pre-Industrial to Industrial times, which spans a range of geologically meaningful [CO2] and δ13Catm values. Δleaf values (carbon isotope discrimination between δ13Catm and δ13Cleaf) remain constant across climate conditions, indicating limited response to environmental stress. Only δ13Cleaf and δ13Catm values showed a strong relationship (linear), thus, δ13Cleaf is an excellent record of carbon isotopic changes in the atmosphere during Industrialization. In contrast with previous free-air concentration enrichment experiments, no relationship was found between C:N ratios and increasing [CO2]. Simultaneously static C:N ratios and Δleaf in light of increasing CO2 highlights plants' inability to match rapid climate change with increased carbon assimilation as previously expected; Δleaf values are not reliable tools to reconstruct MAP and [CO2], and δ13Cleaf values only decrease with [CO2] in line with atmospheric carbon isotope changes.

| S-EPMC6662565 | biostudies-literature

Bevacizumab potentiates chemotherapeutic effect on T-leukemia/lymphoma cells by direct action on tumor endothelial cells.

Project description:Vascular endothelial growth factor-A, an angiogenesis stimulator expressed on both tumor endothelial and malignant T cells, is involved in tumor progression in T-leukemia/lymphoma. Here, we assessed the impact of therapeutic vascular endothelial growth factor-A blockade on tumor-endothelial cell interaction and on tumor progression. In a murine xenograft T-leukemia/lymphoma model, combined bevacizumab (monoclonal antibody against vascular endothelial growth factor-A) with doxorubicin, compared with doxorubicin alone, significantly delayed tumor growth and induced prevalence of tumor cell apoptosis over mitosis. More importantly, the combined treatment induced endothelial cell swelling, microvessel occlusions, and tumor necrosis. In vitro, co-culture of endothelial cells with T-leukemia/lymphoma cells showed that doxorubicin induced expression of intracellular cell adhesion molecule-1, provided endothelial and malignant T cells were in direct contact. This was abrogated by bevacizumab treatment with doxorubicin. Taken together, bevacizumab enhances the chemotherapeutic effect on T-leukemia/lymphoma cells. Directly targeting tumor endothelial cells might be a promising therapeutic strategy to counteract tumor progression in T-cell malignancies.

| S-EPMC3105657 | biostudies-literature

Genetic consequences of fragmentation in "arbor vitae," eastern white cedar (Thuja occidentalis L.), toward the northern limit of its distribution range.

Project description:We tested the hypothesis that marginal fragmented populations of eastern white cedar (EWC) are genetically isolated due to reduced pollen and gene flow. In accordance with the central-marginal model, we predicted a decrease in population genetic diversity and an increase in differentiation along the latitudinal gradient from the boreal mixed-wood to northern coniferous forest. A total of 24 eastern white cedar populations were sampled along the north-south latitudinal gradient for microsatellite genotyping analysis. Positive F(is) values and heterozygote deficiency were observed in populations from the marginal (F(is) = 0.244; P(HW) = 0.0042) and discontinuous zones (F(is) = 0.166; P(HW) = 0.0042). However, populations from the continuous zone were in HW equilibrium (F(is) = -0.007; P(HW) = 0.3625). There were no significant latitudinal effects on gene diversity (H(s)), allelic richness (AR), or population differentiation (F(st)). Bayesian and NJT (neighbor-joining tree) analyses demonstrated the presence of a population structure that was partly consistent with the geographic origins of the populations. The impact of population fragmentation on the genetic structure of EWC is to create a positive inbreeding coefficient, which was two to three times higher on average than that of a population from the continuous zone. This result indicated a higher occurrence of selfing within fragmented EWC populations coupled with a higher degree of gene exchange among near-neighbor relatives, thereby leading to significant inbreeding. Increased population isolation was apparently not correlated with a detectable effect on genetic diversity. Overall, the fragmented populations of EWC appear well-buffered against effects of inbreeding on genetic erosion.

| S-EPMC3492776 | biostudies-literature

Neurotrophic factors: promising candidates in tissue regeneration.

Project description: Not available

| S-EPMC4904460 | biostudies-literature

The Mcm2-7 replicative helicase: a promising chemotherapeutic target.

Project description:Numerous eukaryotic replication factors have served as chemotherapeutic targets. One replication factor that has largely escaped drug development is the Mcm2-7 replicative helicase. This heterohexameric complex forms the licensing system that assembles the replication machinery at origins during initiation, as well as the catalytic core of the CMG (Cdc45-Mcm2-7-GINS) helicase that unwinds DNA during elongation. Emerging evidence suggests that Mcm2-7 is also part of the replication checkpoint, a quality control system that monitors and responds to DNA damage. As the only replication factor required for both licensing and DNA unwinding, Mcm2-7 is a major cellular regulatory target with likely cancer relevance. Mutations in at least one of the six MCM genes are particularly prevalent in squamous cell carcinomas of the lung, head and neck, and prostrate, and MCM mutations have been shown to cause cancer in mouse models. Moreover various cellular regulatory proteins, including the Rb tumor suppressor family members, bind Mcm2-7 and inhibit its activity. As a preliminary step toward drug development, several small molecule inhibitors that target Mcm2-7 have been recently discovered. Both its structural complexity and essential role at the interface between DNA replication and its regulation make Mcm2-7 a potential chemotherapeutic target.

| S-EPMC4163376 | biostudies-literature

Promising new vaccine candidates against Campylobacter in broilers.

Project description:Campylobacter is the leading cause of human bacterial gastroenteritis in the European Union. Birds represent the main reservoir of the bacteria, and human campylobacteriosis mainly occurs after consuming and/or handling poultry meat. Reducing avian intestinal Campylobacter loads should impact the incidence of human diseases. At the primary production level, several measures have been identified to reach this goal, including vaccination of poultry. Despite many studies, however, no efficient vaccine is currently available. We have recently identified new vaccine candidates using the reverse vaccinology strategy. This study assessed the in vivo immune and protective potential of six newly-identified vaccine antigens. Among the candidates tested on Ross broiler chickens, four (YP_001000437.1, YP_001000562.1, YP_999817.1, and YP_999838.1) significantly reduced cecal Campylobacter loads by between 2 and 4.2 log10 CFU/g, with the concomitant development of a specific humoral immune response. In a second trial, cecal load reductions results were not statistically confirmed despite the induction of a strong immune response. These vaccine candidates need to be further investigated since they present promising features.

| S-EPMC5703506 | biostudies-literature

Natural antimicrobial peptides as promising anti-HIV candidates.

Project description:Human immunodeficiency virus type 1 (HIV-1) infection remains to be one of the major global health problems. It is thus necessary to identify novel therapeutic molecules to combat HIV-1. Natural antimicrobial peptides (AMPs) have been recognized as promising templates for developing topical microbicides. This review systematically discusses over 80 anti-HIV peptides annotated in the antimicrobial peptide database (http://aps.unmc.edu/AP). Such peptides have been discovered from bacteria, plants, and animals. Examples include gramicidin and bacteriocins from bacteria, cyclotides from plants, melittins and cecropins from insects, piscidins from fish, ascaphins, caerins, dermaseptins, esculentins, and maximins from amphibians, and cathelicidins and defensins from vertebrates. These peptides appear to work by different mechanisms and could block viral entry in multiple ways. As additional advantages, such anti-HIV peptides may possess other desired features such as antibacterial, antiparasital, spermicidal, and anticancer activity. With continued optimization of peptide stability, production, formulation and delivery methods, it is anticipated that some of these compounds may eventually become new anti-HIV drugs.

| S-EPMC4730921 | biostudies-literature

Acridones as promising drug candidates against Oropouche virus.

Project description:Oropouche virus (OROV) is an emerging vector-borne arbovirus found in South America that causes Oropouche fever, a febrile infection similar to dengue fever. It has a high epidemic potential, causing illness in over 500,000 cases diagnosed since the virus was first discovered in 1955. Currently, the prevention of human viral infection depends on vaccination, but availability for many viruses is limited, and they are classified as neglected viruses. At present, there are no vaccines or antiviral treatments available. An alternative approach to limiting the spread of the virus is to selectively disrupt viral replication mechanisms. Here, we demonstrate the inhibitory effect of acridones, which efficiently inhibited viral replication by 99.9 % in vitro. To evaluate possible mechanisms of action, we conducted tests with dsRNA, an intermediate in virus replication, as well as MD simulations, docking, and binding free energy analysis. The results showed a strong interaction between FAC21 and the OROV endonuclease, which possibly limits the interaction of viral RNA with other proteins. Therefore, our results suggest a dual mechanism of antiviral action, possibly caused by ds-RNA intercalation. In summary, our findings demonstrate that a new generation of antiviral drugs could be developed based on the selective optimization of molecules.

| S-EPMC10792649 | biostudies-literature

Ebola vaccines in clinical trial: The promising candidates.

Project description:Ebola virus disease (EVD) has become a great threat to humans across the world in recent years. The 2014 Ebola epidemic in West Africa caused numerous deaths and attracted worldwide attentions. Since no specific drugs and treatments against EVD was available, vaccination was considered as the most promising and effective method of controlling this epidemic. So far, 7 vaccine candidates had been developed and evaluated through clinical trials. Among them, the recombinant vesicular stomatitis virus-based vaccine (rVSV-EBOV) is the most promising candidate, which demonstrated a significant protection against EVD in phase III clinical trial. However, several concerns were still associated with the Ebola vaccine candidates, including the safety profile in some particular populations, the immunization schedule for emergency vaccination, and the persistence of the protection. We retrospectively reviewed the current development of Ebola vaccines and discussed issues and challenges remaining to be investigated in the future.

| S-EPMC5287303 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data