Update and New Insights on Future Cancer Drug Candidates From Plant-Based Alkaloids.
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ABSTRACT:
SUBMITTER: Tilaoui M
PROVIDER: S-EPMC8716855 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Viral infections are among the most complex medical problems and have been a major threat to the economy and global health. Several epidemics and pandemics have occurred due to viruses, which has led to a significant increase in mortality and morbidity rates. Natural products have always been an inspiration and source for new drug development because of their various uses. Among all-natural sources, plant sources are the most dominant for the discovery of new therapeutic agents due to their chemical and structural diversity. Despite the traditional use and potential source for drug development, natural products have gained little attention from large pharmaceutical industries. Several plant extracts and isolated compounds have been extensively studied and explored for antiviral properties against different strains of viruses. In this review, we have compiled antiviral plant extracts and natural products isolated from plants reported since 2015.
| S-EPMC8537559 | biostudies-literature
Project description:BackgroundThe treatment of non-small-cell lung carcinoma (NSCLC) has changed markedly in recent years as a result of two major treatment milestones: Targeted therapy and immunotherapy. Since 2015, immunotherapy has been changing the paradigm of NSCLC treatment in different settings and has contributed to improve the quality of life of these patients. The most widely used immunotherapy strategy in clinical practice is currently PD-1 and CTLA-4 immune checkpoint inhibition-based immunotherapy. Initial successful results came from an improvement in overall survival for pretreated patients, and immunotherapy subsequently moved to a first-line palliative setting as monotherapy, in combination with chemotherapy or as double-checkpoint inhibition. With regard to earlier stages, consolidation immunotherapy after chemoradiation has also changed the paradigm of unresectable NSCLC, with marked benefits in terms of disease-free and overall survival. During the last few years, efforts have focused on the introduction of immunotherapy in earlier stages as neoadjuvant treatment for potentially resectable tumors and in an adjuvant setting, with some very promising results.AimIn this manuscript, we provide both an agile and thorough review of the role of immunotherapy in non-small cell lung cancer, a critical analysis of the most important studies, current indications, the role of biomarkers, new insights, and future challenges.Relevance for patientsImmunotherapy has revolutionized the treatment of non-small cell lung cancer patients reaching better survival outcomes in first and second palliative setting and in unresectable stage III tumors. Next year's immunotherapy will also introduce in earlier stages. Through an extensive knowledge of the mechanisms of action and of immunotherapy-based studies, the best treatment alternative can be offered to patients, helping to improve their survival and cure rates.
| S-EPMC8177026 | biostudies-literature
Project description:Breast cancer is a major malignancy among women, characterized by a high mortality rate. The available literature evidence indicates that selenium, as a trace element, has chemopreventive properties against many types of cancer; as such, compounds containing it in their structure may potentially exhibit anticancer activity. Accordingly, we have undertaken a study to evaluate the effects of novel selenoesters (EDAG-1, -7, -8, -10) on MCF-7 and MDA-MB-231 breast cancer cells. Our analysis included investigations of cell proliferation and viability as well as cytometric determinations of apoptosis/autophagy induction, changes in mitochondrial membrane polarity (ΔΨm), caspase 3/7, 8, and 9 activities, and Bax, Bcl-2, p53, Akt, AMPK, and LC3A/B proteins. The obtained data revealed that the tested derivatives are highly cytotoxic and inhibit cell proliferation even at nanomolar doses (0.41-0.79 µM). Importantly, their strong proapoptotic properties (↑ caspase 3/7) are attributable to the effects on both the extrinsic (↑ caspase 8) and intrinsic (↓ ΔΨm and Bcl-2, ↑ Bax, p53, and caspase 9) pathways of apoptosis. Moreover, the tested compounds are autophagy activators (↓ Akt, ↑ autophagosomes and autolysosomes, AMPK, LC3A/B). In summary, the potent anticancer activity suggests that the tested compounds may be promising drug candidates for future breast cancer therapy.
| S-EPMC11277004 | biostudies-literature
Project description:The transforming growth factor beta (TGF-β) signaling is fundamental for correct embryonic development. However, alterations of this pathway have been correlated with oncogenesis, tumor progression and sustaining of cancer stem cells (CSCs). Cripto-1 (CR-1) and Nodal are two embryonic proteins involved in TGF-β signaling. Their expression is almost undetectable in terminally differentiated cells, but they are often re-expressed in tumor cells, especially in CSCs. Moreover, cancer cells that show high levels of CR-1 and/or Nodal display more aggressive phenotypes in vitro, while in vivo their expression correlates with a worse prognosis in several human cancers. The ability to target CSCs still represents an unmet medical need for the complete eradication of certain types of tumors. Given the prognostic role and the selective expression of CR-1 and Nodal on cancer cells, they represent archetypes for targeted therapy. The aim of this review is to clarify the role of CR-1 and Nodal in cancer stem populations and to summarize the current therapeutic strategy to target CSCs using monoclonal antibodies (mAbs) or other molecular tools to interfere with these two proteins.
| S-EPMC8345935 | biostudies-literature
Project description: Not available
| S-EPMC11250218 | biostudies-literature
Project description:Drugs currently available for leishmaniasis treatment often show parasite resistance, highly toxic side effects and prohibitive costs commonly incompatible with patients from the tropical endemic countries. In this sense, there is an urgent need for new drugs as a treatment solution for this neglected disease. Here we show the development and implementation of an automated high-throughput viability screening assay for the discovery of new drugs against Leishmania. Assay validation was done with Leishmania promastigote forms, including the screening of 4,000 compounds with known pharmacological properties. In an attempt to find new compounds with leishmanicidal properties, 26,500 structurally diverse chemical compounds were screened. A cut-off of 70% growth inhibition in the primary screening led to the identification of 567 active compounds. Cellular toxicity and selectivity were responsible for the exclusion of 78% of the pre-selected compounds. The activity of the remaining 124 compounds was confirmed against the intramacrophagic amastigote form of the parasite. In vitro microsomal stability and cytochrome P450 (CYP) inhibition of the two most active compounds from this screening effort were assessed to obtain preliminary information on their metabolism in the host. The HTS approach employed here resulted in the discovery of two new antileishmanial compounds, bringing promising candidates to the leishmaniasis drug discovery pipeline.
| S-EPMC2864270 | biostudies-literature
Project description:The overuse of antibiotics in animal agriculture and medicine has caused a series of potential threats to public health. Macleaya cordata is a medicinal plant species from the Papaveraceae family, providing a safe resource for the manufacture of antimicrobial feed additive for livestock. The active constituents from M. cordata are known to include benzylisoquinoline alkaloids (BIAs) such as sanguinarine (SAN) and chelerythrine (CHE), but their metabolic pathways have yet to be studied in this non-model plant. The active biosynthesis of SAN and CHE in M. cordata was first examined and confirmed by feeding 13C-labeled tyrosine. To gain further insights, we de novo sequenced the whole genome of M. cordata, the first to be sequenced from the Papaveraceae family. The M. cordata genome covering 378 Mb encodes 22,328 predicted protein-coding genes with 43.5% being transposable elements. As a member of basal eudicot, M. cordata genome lacks the paleohexaploidy event that occurred in almost all eudicots. From the genomics data, a complete set of 16 metabolic genes for SAN and CHE biosynthesis was retrieved, and 14 of their biochemical activities were validated. These genomics and metabolic data show the conserved BIA metabolic pathways in M. cordata and provide the knowledge foundation for future productions of SAN and CHE by crop improvement or microbial pathway reconstruction.
2017-04-24 | MTBLS435 | MetaboLights
Project description:We present a novel data analysis strategy which combined with subcellular fractionation and liquid chromatography-mass spectrometry (LC-MS) based proteomics provides a simple and effective workflow for global drug profiling. Five subcellular fractions were obtained by differential centrifugation followed by high resolution LC-MS and complete functional regulation analysis. The methodology combines functional regulation and enrichment analysis into a single visual summary. The workflow enables improved insight into perturbations caused by drugs. We provide a statistical argument to demonstrate that even crude subcellular fractions leads to improved functional characterization. We demonstrate this data analysis strategy on data obtained in a MS-based global drug profiling study. However, this strategy can also be performed on other types of large scale biological data.
| S-EPMC4705526 | biostudies-literature
Project description:Solid tumours are the most common cancers and represent a major therapeutic challenge. The cancer stem cell hypothesis is an attractive model to explain the functional heterogeneity commonly observed in solid tumours. It proposes a hierarchical organization of tumours, in which a subpopulation of stem cell-like cells sustains tumour growth, metastasis, and resistance to therapy. We will present the most recent advances in the cancer stem cell field, with particular emphasis on pancreatic cancer as one of the deadliest human tumours, and highlight open questions and caveats to be addressed in future studies. There is increasing evidence that solid tumours including pancreatic cancer are hierarchically organized and sustained by a distinct subpopulation of cancer stem cells. However, direct evidence for the validity of the cancer stem cell hypothesis in human pancreatic cancer remains controversial due to the limitations of xenograft models but supportive data are now emerging from mouse models using related or different sets of markers for the identification of murine cancer stem cells. Therefore, while the clinical relevance of cancer stem cells remains a fundamental issue for this rapidly emerging field, current findings clearly suggest that specific elimination of these cells is possible and therapeutically relevant. Targeting of signalling pathways that are of particular importance for the maintenance and the elimination of cancer stem cell as the proposed root of the tumour may lead to the development of novel treatment regimens for pancreatic cancer. Here we will review the current literature on pancreatic cancer stem cells and the future perspective of this rapidly emerging field.
| S-EPMC5527928 | biostudies-other
Project description:BackgroundsPolycystic ovary syndrome affects 7% of women of reproductive ages. Poor-quality oocytes, along with lower cleavage and implantation rates, reduce fertilization.ObjectiveThis study aimed to determine crucial molecular mechanisms behind PCOS pathogenesis and repurpose new drug candidates interacting with them. To predict a more in-depth insight, we applied a novel bioinformatics approach to analyze interactions between the drug-related and PCOS proteins in PCOS patients.MethodsThe newest proteomics data was retrieved from 16 proteomics datasets and was used to construct the PCOS PPI network using Cytoscape. The topological network analysis determined hubs and bottlenecks. The MCODE Plugin was used to identify highly connected regions, and the associations between PCOS clusters and drug-related proteins were evaluated using the Chi-squared/Fisher's exact test. The crucial PPI hub-bottlenecks and the shared molecules (between the PCOS clusters and drug-related proteins) were then investigated for their drug-protein interactions with previously US FDA-approved drugs to predict new drug candidates.ResultsThe PI3K/AKT pathway was significantly related to one PCOS subnetwork and most drugs (metformin, letrozole, pioglitazone, and spironolactone); moreover, VEGF, EGF, TGFB1, AGT, AMBP, and RBP4 were identified as the shared proteins between the PCOS subnetwork and the drugs. The shared top biochemical pathways between another PCOS subnetwork and rosiglitazone included metabolic pathways, carbon metabolism, and citrate cycle, while the shared proteins included HSPB1, HSPD1, ACO2, TALDO1, VDAC1, and MDH2. We proposed some new candidate medicines for further PCOS treatment investigations, such as copper and zinc compounds, reteplase, alteplase, gliclazide, Etc.ConclusionSome of the crucial molecules suggested by our model have already been experimentally reported as critical molecules in PCOS pathogenesis. Moreover, some repurposed medications have already shown beneficial effects on infertility treatment. These previous experimental reports confirm our suggestion for investigating our other repurposed drugs (in vitro and in vivo).
| S-EPMC8416576 | biostudies-literature