Apoptosis-like cell death upon kinetoplastid induction by compounds isolated from the brown algae Dictyota spiralis.
Ontology highlight
ABSTRACT: Background
The in vitro activity of the brown seaweed Dictyota spiralis against both Leishmania amazonensis and Trypanosoma cruzi was evaluated in a previous study. Processing by bio-guided fractionation resulted in the isolation of three active compounds, classified as diterpenes. In the present study, we performed several assays to detect clinical features associated to cell death in L. amazonensis and T. cruzi with the aim to elucidate the mechanism of action of these compounds on parasitic cells.Methods
The aims of the experiments were to detect and evaluate specific events involved in apoptosis-like cell death in the kinetoplastid, including DNA condensation, accumulation of reactive oxygen species and changes in ATP concentration, cell permeability and mitochondrial membrane potential, respectively, in treated cells.Results
The results demonstrated that the three isolated diterpenes could inhibit the tested parasites by inducing an apoptosis-like cell death.Conclusions
These results encourage further investigation on the isolated compounds as potential drug candidates against both L. amazonensis and T. cruzi.
SUBMITTER: Chiboub O
PROVIDER: S-EPMC8042727 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Bioassay-guided fractionation of the antikinetoplastid extract of the brown alga Dictyota spiralis has led to the isolation of spiralyde A (1), a new dolabellane aldehyde, along with other five known related diterpenes (2⁻6). Their structures were determined by HRESIMS, 1D and 2D NMR spectroscopy, and comparison with data reported in the literature. The antiparasitic activity of all compounds was evaluated. Spiralyde A (1) and the known compound 3,4-epoxy-7,18-dolabelladiene (2) were the most active compounds against Leishmania amazonensis and Trypanosoma cruzi. Spiralyde A (1) was the most potent compound, comparable to benznidazole, the reference drug for trypanocidal activity.
| S-EPMC6471066 | biostudies-other
Project description:The aim of this study was to investigate the anticancer and antioxidant activities as well as the safety of the brown algae Dictyota dichotoma of the Western seacoast of Yemen. Cytotoxicity of methanol extract of D. dichotoma and several of its fractions, petroleum ether, chloroform, ethyl acetate, n-butanol, and aqueous extracts against seven different cancer cell lines was determined by crystal violet staining. The antioxidant activity was also assessed using the DPPH radical scavenging assay. Acute toxicity study was performed on rats at increasing doses of the methanol extract. Extracts of D. dichotoma exerted a significant dose-dependent cytotoxicity on the seven tumor cell lines but were generally more selective on MCF-7 and PC-3. Among all fractions, the chloroform fraction of the D. dichotoma displayed the highest cytotoxic activity and was most effective in MCF-7, PC3, and CACO cells (IC50?=?1.93?±?0.25, 2.2?±?0.18, and 2.71?±?0.53??g/mL, respectively). The petroleum ether fraction was also effective, particularly against MCF-7 and PC-3 (IC50?=?4.77?±?0.51 and 3.93?±?0.51??g/mL, respectively) whereas the activity of the ethyl acetate fraction was more pronounced against HepG2 and CACO (IC50?=?5.06?±?0.21 and 5.06?±?0.23??g/mL, respectively). Of all the extracts tested, the crude methanolic extract of the algae exhibited only a modest antioxidant potential (IC50?=?204.6?±?8.3??g/mL). Doses as high as 5000?mg/kg body weight of D. dichotoma methanolic extracts were safe and well tolerated by rats. The overall results showed that D. dichotoma exhibited a significant cytotoxic activity probably due to the occurrence of nonpolar cytotoxic compounds, which is independent of its antioxidant capability.
| S-EPMC7048913 | biostudies-literature
Project description:BackgroundHybridization or divergence between sympatric sister species provides a natural laboratory to study speciation processes. The shared polymorphism in sister species may either be ancestral or derive from hybridization, and the accuracy of analytic methods used thus far to derive convincing evidence for the occurrence of present day hybridization is largely debated.ResultsHere we propose the application of network analysis to test for the occurrence of present day hybridization between the two species of brown algae Fucus spiralis and F. vesiculosus. Individual-centered networks were analyzed on the basis of microsatellite genotypes from North Africa to the Pacific American coast, through the North Atlantic. Two genetic distances integrating different time steps were used, the Rozenfeld (RD; based on alleles divergence) and the Shared Allele (SAD; based on alleles identity) distances. A diagnostic level of genotype divergence and clustering of individuals from each species was obtained through RD while screening for exchanges through putative hybridization was facilitated using SAD. Intermediate individuals linking both clusters on the RD network were those sampled at the limits of the sympatric zone in Northwest Iberia.ConclusionThese results suggesting rare hybridization were confirmed by simulation of hybrids and F2 with directed backcrosses. Comparison with the Bayesian method STRUCTURE confirmed the usefulness of both approaches and emphasized the reliability of network analysis to unravel and study hybridization.
| S-EPMC3040711 | biostudies-literature
Project description:The levels and composition of sphingolipids and related metabolites are altered in aging and in common disorders such as diabetes and cancers, as well as in neurodegenerative, cardiovascular, and respiratory diseases. Changes in sphingolipids have been implicated as being an essential step in mitochondria-driven cell death. However, little is known about the precise sphingolipid composition and modulation in mitochondria or related organelles. Here, we used LC-MS/MS to analyze the presence of key components of the ceramide metabolic pathway in vivo and in vitro in purified ER, mitochondria-associated membranes (MAMs), and mitochondria. Specifically, we analyzed the sphingolipids in the three pathways that generate ceramide: sphinganine in the de novo ceramide pathway, SM in the breakdown pathway, and sphingosine in the salvage pathway. We observed sphingolipid profiles in mouse liver, mouse brain, and a human glioma cell line (U251). We analyzed the quantitative and qualitative changes of these sphingolipids during staurosporine-induced apoptosis in U251 cells. Ceramide (especially C16-ceramide) levels increased during early apoptosis possibly through a conversion from mitochondrial sphinganine and SM, but sphingosine and lactosyl- and glycosyl-ceramide levels were unaffected. We also found that ceramide generation is enhanced in mitochondria when SM levels are decreased in the MAM. This decrease was associated with an increase in acid sphingomyelinase activity in MAM. We conclude that meaningful sphingolipid modifications occur in MAM, the mitochondria, and the ER during the early steps of apoptosis.
| S-EPMC7328052 | biostudies-literature
Project description:Rapidly proliferating cells, such as cancer cells, have adopted aerobic glycolysis rather than oxidative phosphorylation to supply their energy demand; this phenomenon is known as 'the Warburg effect'. It is now widely accepted that during apoptosis the loss of energy production, orchestrated by caspases, contributes to the dismantling of the dying cell. However, how this loss of energy production occurs is still only partially known. In the present work, we established that during apoptosis the level of cellular ATP decreased in a caspase-dependent manner. We demonstrated that this decrease in ATP content was independent of any caspase modification of glucose uptake, ATP consumption or reactive oxygen species production but was dependent on a caspase-dependent inhibition of glycolysis. We found that the activity of the two glycolysis-limiting enzymes, phosphofructokinase and pyruvate kinase, were affected by caspases, whereas the activity of phosphoglycerate kinase was not, suggesting specificity of the effect. Finally, using a metabolomic analysis, we observed that caspases led to a decrease in several key metabolites, including phosphoserine, which is a major regulator of pyruvate kinase muscle isozyme activity. Thus, we have established that during apoptosis, caspases can shut down the main energy production pathway in cancer cells, leading to the impairment in the activity of the two enzymes controlling limiting steps of glycolysis.
| S-EPMC4540195 | biostudies-literature
Project description:The marine brown alga Dictyota pfaffii from Atol das Rocas, in Northeast Brazil is a rich source of dolabellane diterpene, which has the potential to be used in future antiviral drugs by inhibiting reverse transcriptase (RT) of HIV-1. Reexamination of the minor diterpene constituents yielded three new dolabellane diterpenes, (1R*,2E,4R*,7S,10S*,11S*,12R*)10,18-diacetoxy-7-hydroxy-2,8(17)-dolabelladiene (1), (1R*,2E,4R*,7R*,10S*,11S*,12R*)10,18-diacetoxy-7-hydroxy-2,8(17)-dolabelladiene (2), (1R*,2E,4R*,8E,10S*,11S,12R*)10,18-diacetoxy-7-hydroxy-2,8-dolabelladiene (3), termed dolabelladienols A-C (1-3) respectively, in addition to the known dolabellane diterpenes (4-6). The elucidation of the compounds 1-3 was assigned by 1D and 2D NMR, MS, optical rotation and molecular modeling, along with the relative configuration of compound 4 and the absolute configuration of 5 by X-ray diffraction. The potent anti-HIV-1 activities displayed by compounds 1 and 2 (IC50 = 2.9 and 4.1 ?M), which were more active than even the known dolabelladienetriol 4, and the low cytotoxic activity against MT-2 lymphocyte tumor cells indicated that these compounds are promising anti-HIV-1 agents.
| S-EPMC4113826 | biostudies-other
Project description:The aim of this study was to reveal the biological activities and in vivo toxicity profiles of n-hexane, chloroform and methanol extracts of brown algae Halopteris scoparia L. Sauvageau. In this study, extracts were tested for their phytochemical contents and antioxidant activities. The cytotoxic activities of the extracts against cervical adenocarcinoma (HeLa), colon colorectal adenocarcinoma (CaCo-2) and breast adenocarcinoma (MCF7) cells were assessed by MTT assay and total RNAs derived from cell lines to analyze gene expression were analyzed by Real Time Ready Human Apoptosis Panel 96. Also, in vivo toxicity and irritation effects of extracts were evaluated by LD50 acute toxicity test and Hen's egg test chorioallantoic membrane (HET-CAM) assay, respectively. Our results showed that the phenolic and flavonoid contents were determined only in methanol extract (33.20?±?1.41 mg GAE/g and 1.26?±?0.95 mg QE/g). Also, n-hexane has a broader spectrum of content than methanol and chloroform extracts. Furthermore, n-hexane extract in DPPH and methanol extract in ABTS+ exhibited the best antioxidant activity. In addition, MTT results revealed that each three extracts cause a significant reduction in cell viability, especially in HeLa cells. When the apoptotic gene expressions were examined after treatment of extracts, the expression of many pro-apoptotic genes in both caspase-independent and caspase-dependent intrinsic and extrinsic pathways increased. These findings suggest that, considering that it had not led to irritation and toxicity in vivo, edible H. scoparia is a natural antioxidant and its apoptotic/cytotoxic activities can potentially be used against human cancers.
| S-EPMC6546795 | biostudies-literature
Project description:Marine algae are an important source of bioactive metabolites in drug development and nutraceuticals. Diabetes mellitus is a metabolic disorder and the third leading cause of death worldwide due to lifestyle changes associated with rapid urbanization. Due to the adverse side effects of currently available antidiabetic drugs, search for an effective natural-based antidiabetic drug is important to combat diabetes and its complications. Therefore, in lieu with herbal drug development, it is important to find the potential benefits of seaweeds for the management of type 2 diabetes as they are underexplored yet in Sri Lanka. Among the marine seaweeds, natural bioactive compounds are abundant in brown algae with potentials in application as active ingredients in drug leads and nutraceuticals. Bioactive secondary metabolites are derived from numerous biosynthetic pathways of marine algae which contribute to various chemical and biological properties. Phlorotannins present in marine brown algae exhibited antidiabetic activities through different mechanisms such as the inhibitory effect of enzyme targets mainly by inhibiting the enzymes such as ?-amylase, ?-glucosidase, angiotensin-converting enzymes (ACE), aldose reductase, dipeptidyl peptidase-4, and protein tyrosine phosphatase 1B (PTP 1B) enzyme. In addition, phlorotannins derived from brown algae have the ability to reduce diabetic complications. Hence, the present review focuses on the different antidiabetic mechanisms of secondary bioactive compounds present in marine brown algae.
| S-EPMC7197011 | biostudies-literature
Project description:Cell walls of the brown algae contain a diverse range of polysaccharides with useful bioactivities. The precise structures of the sulfated fucan/fucoidan group of polysaccharides and their roles in generating cell wall architectures and cell properties are not known in detail. Four rat monoclonal antibodies, BAM1 to BAM4, directed to sulfated fucan preparations, have been generated and used to dissect the heterogeneity of brown algal cell wall polysaccharides. BAM1 and BAM4, respectively, bind to a non-sulfated epitope and a sulfated epitope present in the sulfated fucan preparations. BAM2 and BAM3 identified additional distinct epitopes present in the fucoidan preparations. All four epitopes, not yet fully characterised, occur widely within the major brown algal taxonomic groups and show divergent distribution patterns in tissues. The analysis of cell wall extractions and fluorescence imaging reveal differences in the occurrence of the BAM1 to BAM4 epitopes in various tissues of Fucus vesiculosus. In Ectocarpus subulatus, a species closely related to the brown algal model Ectocarpus siliculosus, the BAM4 sulfated epitope was modulated in relation to salinity levels. This new set of monoclonal antibodies will be useful for the dissection of the highly complex and yet poorly resolved sulfated polysaccharides in the brown algae in relation to their ecological and economic significance.
| S-EPMC4333822 | biostudies-literature
Project description:Stringent searches for microRNAs (miRNAs) have so far only identified these molecules in animals, land plants, chlorophyte green algae, slime molds and brown algae. The identification of miRNAs in brown algae was based on the analysis of a single species, the filamentous brown alga Ectocarpus sp. Here, we have used deep sequencing of small RNAs and a recently published genome sequence to identify miRNAs in a second brown alga, the kelp Saccharina japonica. S. japonica possesses a large number of miRNAs (117) and these miRNAs are highly diverse, falling into 98 different families. Surprisingly, none of the S. japonica miRNAs share significant sequence similarity with the Ectocarpus sp. miRNAs. However, the miRNA repertoires of the two species share a number of structural and genomic features indicating that they were generated by similar evolutionary processes and therefore probably evolved within the context of a common, ancestral miRNA system. This lack of sequence similarity suggests that miRNAs evolve rapidly in the brown algae (the two species are separated by ∼95 Myr of evolution). The sets of predicted targets of miRNAs in the two species were also very different suggesting that the divergence of the miRNAs may have had significant consequences for miRNA function.
| S-EPMC5381526 | biostudies-literature