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Marine Drugs Jun 2024The marine environment provides a rich source of distinct creatures containing potentially revolutionary bioactive chemicals. One of these organisms is , a type of green...
Green Seaweed as a Novel Non-Small Cell Lung Cancer Inhibitor in Overcoming Tyrosine Kinase Inhibitor Resistance: An Analysis Employing Network Pharmacology, Molecular Docking, and In Vitro Research.
The marine environment provides a rich source of distinct creatures containing potentially revolutionary bioactive chemicals. One of these organisms is , a type of green algae known as green seaweed, seagrapes, or green caviar. This organism stands out because it has great promise for use in medicine, especially in the study of cancer. Through the utilization of computational modeling (in silico) and cellular laboratory experiments (in vitro), the chemical components included in the green seaweed were effectively analyzed, uncovering its capability to treat non-small cell lung cancer (NSCLC). The study specifically emphasized blocking SRC, STAT3, PIK3CA, MAPK1, EGFR, and JAK1 using molecular docking and in vitro. These proteins play a crucial role in the EGFR Tyrosine Kinase Inhibitor Resistance pathway in NSCLC. The chemical Caulersin (C2) included in extract (CRE) has been identified as a potent and effective agent in fighting against non-small cell lung cancer (NSCLC), both in silico and in vitro. CRE and C2 showed a level of inhibition similar to that of osimertinib (positive control/NSCLC drug).
Topics: Humans; Molecular Docking Simulation; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Protein Kinase Inhibitors; Caulerpa; Drug Resistance, Neoplasm; Network Pharmacology; Cell Line, Tumor; Seaweed; Antineoplastic Agents; Plant Extracts; ErbB Receptors; Acrylamides; Tyrosine Kinase Inhibitors
PubMed: 38921583
DOI: 10.3390/md22060272 -
Frontiers in Immunology 2024Colorectal cancer exhibits a notable prevalence and propensity for metastasis, but the current therapeutic interventions for metastatic colorectal cancer have yielded... (Review)
Review
Colorectal cancer exhibits a notable prevalence and propensity for metastasis, but the current therapeutic interventions for metastatic colorectal cancer have yielded suboptimal results. ICIs can decrease tumor development by preventing the tumor's immune evasion, presenting cancer patients with a new treatment alternative. The increased use of immune checkpoint inhibitors (ICIs) in CRC has brought several issues. In particular, ICIs have demonstrated significant clinical effectiveness in patients with MSI-H CRC, whereas their efficacy is limited in MSS. Acquired resistance can still occur in patients with a positive response to ICIs. This paper describes the efficacy of ICIs currently in the clinical treatment of CRC, discusses the mechanisms by which acquired resistance occurs, primarily related to loss and impaired presentation of tumor antigens, reduced response of IFN-λ and cytokine or metabolic dysregulation, and summarizes the incidence of adverse effects. We posit that the future of ICIs hinges upon the advancement of precise prediction biomarkers and the implementation of combination therapies. This study aims to elucidate the constraints associated with ICIs in CRC and foster targeted problem-solving approaches, thereby enhancing the potential benefits for more patients.
Topics: Humans; Colorectal Neoplasms; Immune Checkpoint Inhibitors; Animals; Drug Resistance, Neoplasm
PubMed: 38919624
DOI: 10.3389/fimmu.2024.1403533 -
Scientific Reports Jun 2024Sphaeropsidins are iso-pimarane diterpenes produced by phytopathogenic fungi that display promising anticancer activities. Sphaeropsidin A, in particular, has been shown...
Sphaeropsidins are iso-pimarane diterpenes produced by phytopathogenic fungi that display promising anticancer activities. Sphaeropsidin A, in particular, has been shown to counteract regulatory volume increase, a process used by cancer cells to avoid apoptosis. This study reports the hemi-synthesis of new lipophilic derivatives obtained by modifications of the C15,C16-alkene moiety. Several of these compounds triggered severe ER swelling associated with strong proteasomal inhibition and consequently cell death, a feature that was not observed with respect to mode of action of the natural product. Significantly, an analysis from the National Cancer Institute sixty cell line testing did not reveal any correlations between the most potent derivative and any other compound in the database, except at high concentrations (LC). This study led to the discovery of a new set of sphaeropsidin derivatives that may be exploited as potential anti-cancer agents, notably due to their maintained activity towards multidrug resistant models.
Topics: Humans; Endoplasmic Reticulum; Cell Line, Tumor; Apoptosis; Antineoplastic Agents; Diterpenes; Abietanes
PubMed: 38918539
DOI: 10.1038/s41598-024-65335-3 -
Frontiers in Chemistry 2024Numerous local herbal extract species have been investigated as potential medicinal ingredients due to their promising anti-cancer properties. However, the primary...
Numerous local herbal extract species have been investigated as potential medicinal ingredients due to their promising anti-cancer properties. However, the primary constraint of the class of plant flavonoids lies in their low solubility and limited membrane permeability, leading to chemical instability and restricted bioavailability that impede biomedical applications. In this study, we have developed an ideal nanozyme-Galazyme, comprising galangin-loaded copper Nanozyme coated by DSPE-PEG, which amplifies oxidative stress to induce apoptosis via the regulation of reactive oxygen species (ROS) generation and mitogen-activated protein kinase (MAPK) activation. Galazyme exhibited significant peroxidase mimetic activity, demonstrating its potential to generate ROS and elevate oxidative stress. Upon uptake by HepG-2 cells, Galazyme efficiently converts excess hydrogen peroxide (H2O2) into highly reactive •OH radicals and upregulates MAPK expression, leading to the activation of Bax and Caspase 3, thereby promoting irreversible tumor cell apoptosis. Both and results demonstrate that Galazyme inhibits tumor cell growth and induces apoptosis by generating ample ROS and activating the MAPK pathway. Our study offers novel evidence supporting the enhancement of Galazyme-induced apoptosis through the upregulation of Bax and Caspase 3, along with the elucidation of the interaction between MAPK and apoptosis.
PubMed: 38915904
DOI: 10.3389/fchem.2024.1426634 -
Scientific Reports Jun 2024Cryptosporidiosis is a worldwide zoonotic disease. Oxymatrine, an alkaloid extracted and isolated from the plant bitter ginseng, has been reported to have therapeutic...
Cryptosporidiosis is a worldwide zoonotic disease. Oxymatrine, an alkaloid extracted and isolated from the plant bitter ginseng, has been reported to have therapeutic effects on cryptosporidiosis. However, the underlying mechanism of its action remains unclear. In this study, we utilized network pharmacology and experimental validation to investigate the mechanism of oxymatrine in the treatment of cryptosporidiosis. First, the potential targets of drugs and diseases were predicted by TCMSP, Gene Cards, and other databases. Following the intersection of drug-disease targets, the DAVID database was used to implement the enrichment analysis of GO functions and KEGG pathways, and then the network diagram of "intersected target-KEGG" relationship was constructed. Autodock 4.2.6 software was used to carry out the molecular docking of core targets to drug components. Based on the establishment of a mouse model of cryptosporidiosis, the validity of the targets in the TNF/NF-κB signaling pathway was confirmed using Western blot analysis and Quantitative Rea-ltime-PCR. A total of 41 intersectional targets of oxymatrine and Cryptosporidium were generated from the results, and five core targets were screened out by network analysis, including RELA, AKT1, ESR1, TNF, and CASP3. The enrichment analysis showed that oxymatrine could regulate multiple gene targets, mediate TNF, Apoptpsis, IL-17, NF-κB and other signaling pathways. Molecular docking experiments revealed that oxymatrine was tightly bound to core targets with stable conformation. Furthermore, we found through animal experiments that oxymatrine could regulate the mRNA and protein expression of IL-6, NF-κB, and TNF-α in the intestinal tissues of post-infected mice through the TNF/NF-κB signaling pathway. Therefore, it can be concluded that oxymatrine can regulate the inflammatory factors TNF-α, NF-κB, and IL-6 through the TNF/NF-κB signaling pathway for the treatment of cryptosporidiosis. This prediction has also been validated by network pharmacology and animal experiments.
Topics: Quinolizines; Cryptosporidiosis; Animals; Signal Transduction; Alkaloids; Mice; NF-kappa B; Network Pharmacology; Molecular Docking Simulation; Tumor Necrosis Factor-alpha; Disease Models, Animal; Humans; Matrines
PubMed: 38914662
DOI: 10.1038/s41598-024-65362-0 -
Frontiers in Pharmacology 2024Lung cancer is the most commonly diagnosed and the main cause of cancer death, usually related to cigarette smoking. Furthermore, the microbiota of people exposed to...
INTRODUCTION
Lung cancer is the most commonly diagnosed and the main cause of cancer death, usually related to cigarette smoking. Furthermore, the microbiota of people exposed to cigarette smoke can be modified, making it difficult to eliminate opportunistic microorganisms. The leaves of are a by-product of fruit production and, to date, there have been no studies addressing the antiproliferative, anti-inflammatory, and antimicrobial activities.
OBJECTIVE
Investigate the antimicrobial, Nitric Oxide (NO)-production inhibition, and antiproliferative activities of the essential oil from leaves and its possible effect on the treatment and prevention of damage caused by tobacco.
METHODS
The essential oil (EO) was obtained by hydrodistillation (3 h). Its chemical composition was investigated by GC-MS. It was proposed to investigate antiproliferative activity against human tumor cell lines, namely, breast adenocarcinoma (MCF-7), lung (NCI-H460), cervical (HeLa), and hepatocellular (HepG2) carcinomas. A non-tumor primary culture from pig liver (PLP2) was also tested. The EO capacity to inhibit nitric oxide (NO) production was evaluated by a lipopolysaccharide stimulated murine macrophage cell line. Antibacterial and antifungal activities against opportunistic pathogens were investigated against seven strains of bacteria and eight fungi.
RESULTS
The results indicated the presence of 23 compounds in the essential oil, the majority were spathulenol (45.63%) and β-caryophyllene oxide (12.72%). Leaf EO provided 50% inhibition of nitric oxide production at a concentration of 92.04 µg mL. The EO also demonstrated antiproliferative activity against all human tumor cell lines studied, with GI50 values comprised between 270.86 and 337.25 µg mL. The essential oil showed antimicrobial potential against the bacteria monocytogenes (Murray et al.) Pirie (NCTC 7973) and ATCC 13311 (MIC 1870 µg mL) and fungi ATCC 11730, ATCC 12066, ATCC 90288, var. cyclopium (Westling) Samson, Stolk & Hadlok (food isolate) (MIC 1870 µg mL) and Pers. IAM 5061 (1,400 µg mL).
CONCLUSION
The demonstrated anti-inflammatory, antiproliferative, and antimicrobial activities in the leaves of can add value to the production chain of this plant, being a possible option for preventing and combating cancer, including lung cancer.
PubMed: 38910894
DOI: 10.3389/fphar.2024.1415659 -
Scientific Reports Jun 2024Breast cancer (BC) remains a significant health concern for women globally, prompting the relentless pursuit of novel therapeutic modalities. As a traditional Chinese...
Breast cancer (BC) remains a significant health concern for women globally, prompting the relentless pursuit of novel therapeutic modalities. As a traditional Chinese medicine, Boswellia carterii has been extensively used to treat various cancers, such as BC. However, the anti-BC effect and underlying mechanism of Boswellia carterii remain largely unclear. The aim of this study is to explore the therapeutic effect of Boswellia carterii n-hexane extract (BCHE) against BC as well as its underlying mechanism. The present study showed that BCHE significantly suppressed the viability of human BC cells. Moreover, BCHE exhibited potent anti-BC activity in vivo with no significant toxic effects. Additionally, BCHE induced ferroptosis via increased Transferrin expression and the intracellular accumulation of Fe, as well as decreased glutathione peroxidase 4 (GPX4) expression and the upregulation of reactive oxygen species (ROS)-induced lipid peroxidation in BC cells. In vivo experimental results also demonstrated that BCHE effectively induced ferroptosis through GPX4 downregulation and Transferrin upregulation in tumor-bearing mice. Overall, BCHE inhibited the growth of BC cells by inducing ferroptosis mediated by modulating the iron accumulation pathway and the lipid peroxidation pathway. Therefore, BCHE could serve as a potential ferroptosis-targeting drug for treating BC.
Topics: Ferroptosis; Phospholipid Hydroperoxide Glutathione Peroxidase; Humans; Breast Neoplasms; Female; Animals; Transferrin; Mice; Plant Extracts; Cell Line, Tumor; Boswellia; Reactive Oxygen Species; Xenograft Model Antitumor Assays; Cell Proliferation; Hexanes; Down-Regulation; Lipid Peroxidation; Up-Regulation; Gene Expression Regulation, Neoplastic; Mice, Nude; Mice, Inbred BALB C
PubMed: 38906931
DOI: 10.1038/s41598-024-65170-6 -
Frontiers in Plant Science 2024Clubroot disease, which is caused by the obligate biotrophic protist , leads to the formation of galls, commonly known as pathogen-induced tumors, on the roots of...
Clubroot disease, which is caused by the obligate biotrophic protist , leads to the formation of galls, commonly known as pathogen-induced tumors, on the roots of infected plants. The identification of crucial regulators of host tumor formation is essential to unravel the mechanisms underlying the proliferation and differentiation of within plant cells. To gain insight into this process, transcriptomic analysis was conducted to identify key genes associated with both primary and secondary infection of in Chinese cabbage. Our results demonstrate that the k-means clustering of subclass 1, which exhibited specific trends, was closely linked to the infection process of . Of the 1610 differentially expressed genes (DEGs) annotated in subclass 1, 782 were identified as transcription factors belonging to 49 transcription factor families, including bHLH, B3, NAC, MYB_related, WRKY, bZIP, C2H2, and ERF. In the primary infection, several genes, including the predicted probable pectate lyase, RPM1-interacting protein 4-like, L-type lectin-domain-containing receptor kinase, G-type lectin S-receptor-like serine, photosystem II 22 kDa protein, and MLP-like protein, showed significant upregulation. In the secondary infection stage, 45 of 50 overlapping DEGs were upregulated. These upregulated DEGs included the predicted endoglucanase, long-chain acyl-CoA synthetase, WRKY transcription factor, NAC domain-containing protein, cell division control protein, auxin-induced protein, and protein variation in compound-triggered root growth response-like and xyloglucan glycosyltransferases. In both the primary and secondary infection stages, the DEGs were predicted to be putative disease resistance proteins, L-type lectin domain-containing receptor kinases, ferredoxin-NADP reductases, 1-aminocyclopropane-1-carboxylate synthases, histone deacetylases, UDP-glycosyltransferases, putative glycerol-3-phosphate transporters, and chlorophyll a-binding proteins, which are closely associated with plant defense responses, biosynthetic processes, carbohydrate transport, and photosynthesis. This study revealed the pivotal role of transcription factors in the initiation of infection and establishment of intracellular parasitic relationships during the primary infection stage, as well as the proliferation and differentiation of the pathogen within the host cell during the secondary infection stage.
PubMed: 38903421
DOI: 10.3389/fpls.2024.1391173 -
Molecular Medicine (Cambridge, Mass.) Jun 2024Despite recent advances in tumor diagnosis and treatment technologies, the number of cancer cases and deaths worldwide continues to increase yearly, creating an urgent... (Review)
Review
Despite recent advances in tumor diagnosis and treatment technologies, the number of cancer cases and deaths worldwide continues to increase yearly, creating an urgent need to find new methods to prevent or treat cancer. Sulforaphane (SFN), as a member of the isothiocyanates (ITCs) family, which is the hydrolysis product of glucosinolates (GLs), has been shown to have significant preventive and therapeutic cancer effects in different human cancers. Early studies have shown that SFN scavenges oxygen radicals by increasing cellular defenses against oxidative damage, mainly through the induction of phase II detoxification enzymes by nuclear factor erythroid 2-related factor 2 (Nrf2). More and more studies have shown that the anticancer mechanism of SFN also includes induction of apoptotic pathway in tumor cells, inhibition of cell cycle progression, and suppression of tumor stem cells. Therefore, the application of SFN is expected to be a necessary new approach to treating cancer. In this paper, we review the multiple molecular mechanisms of SFN in cancer prevention and treatment in recent years, which can provide a new vision for cancer treatment.
Topics: Isothiocyanates; Sulfoxides; Humans; Neoplasms; Anticarcinogenic Agents; Animals; Apoptosis; NF-E2-Related Factor 2
PubMed: 38902597
DOI: 10.1186/s10020-024-00842-7 -
Scientific Reports Jun 2024Natural products are an unsurpassed source of leading structures in drug discovery. The biosynthetic machinery of the producing organism offers an important source for...
Natural products are an unsurpassed source of leading structures in drug discovery. The biosynthetic machinery of the producing organism offers an important source for modifying complex natural products, leading to analogs that are unattainable by chemical semisynthesis or total synthesis. In this report, through the combination of natural products chemistry and diversity-oriented synthesis, a diversity-enhanced extracts approach is proposed using chemical reactions that remodel molecular scaffolds directly on extracts of natural resources. This method was applied to subextract enriched in sesquiterpene lactones from Ambrosia tenuifolia (Fam. Asteraceae) using acid media conditions (p-toluenesulfonic acid) to change molecular skeletons. The chemically modified extract was then fractionated by a bioguided approach to obtain the pure compounds responsible for the anti-glioblastoma (GBM) activity in T98G cell cultures. Indeed, with the best candidate, chronobiological experiments were performed to evaluate temporal susceptibility to the treatment on GBM cell cultures to define the best time to apply the therapy. Finally, bioinformatics tools were used to supply qualitative and quantitative information on the physicochemical properties, chemical space, and structural similarity of the compound library obtained. As a result, natural products derivatives containing new molecular skeletons were obtained, with possible applications as chemotherapeutic agents against human GBM T98G cell cultures.
Topics: Humans; Glioblastoma; Cell Line, Tumor; Plant Extracts; Antineoplastic Agents, Phytogenic; Biological Products; Asteraceae; Sesquiterpenes; Lactones; Antineoplastic Agents
PubMed: 38902325
DOI: 10.1038/s41598-024-63639-y