Search Results (167)

Taxanes represent a crucial class of chemotherapeutic agents clinically employed for the treatment of various malignancies, including breast cancer. Three commonly utilized taxanes—paclitaxel (Taxol), docetaxel (Taxotere), and cabazitaxel—are substantially limited by inherent drawbacks such as poor aqueous solubility, rapid clearance, and non-specific distribution. To enhance their anti-tumor efficacy against breast cancer, an mPEG-PLA-(LA)₄ nanomicelle carrier was designed and synthesized in this study for the loading of these three taxanes. These nanomicelles were designed to improve the aqueous compatibility and nanomicelle-mediated delivery of hydrophobic taxanes. In vivo animal experiments were conducted to evaluate the therapeutic effects of the three drug-loaded nanomicelles on subcutaneous human breast cancer MCF-7 xenografts in BALB/c nude mice. The results demonstrated that the injectable paclitaxel, docetaxel, and cabazitaxel micelles exhibited significant inhibitory effects on the MCF-7 xenograft tumors. These findings suggest that mPEG-PLA-(LA)₄ DS nanomicelles may serve as a structurally defined and versatile carrier platform for hydrophobic taxane delivery. Full article

Relict yew plants (Taxus L.) are not only ornamental plants with valuable wood but also have the ability to synthesize the unique compound taxol, which is successfully used in the treatment of cancer due to its powerful cytotoxic effect. Due to the presence of taxol, all parts of yew plants are extremely poisonous, but there have been cases where animals have eaten yew cones without fatal consequences. The biosynthesis of taxol is carried out due to the interaction of the isoprenoid and phenolic pathways of the secondary metabolism of plants. Despite the close attention of researchers to the peculiarities of taxol metabolism, there is very little data on the tissue and intracellular localization of both taxols and phenolic compounds in yew plants. Polyphenols are known to be physiologically active mediators involved in respiration, photosynthesis, plant growth and development, as well as in the process of in vitro dedifferentiation. Since Taxus is a relict species and has a limited and hard-to-reach range in nature, technologies that allow yew plants to be restored without removing plant material from the natural environment are of great practical importance: overcoming deep physiological dormancy of seeds, microclonal reproduction and initiation of plant growth. In vitro cultures are possible sources of biologically active and medicinal products. The aims and objectives of this study are to determine the characteristics of the formation and localization of phenolic compounds with high biological activity in various organs of plants of the genus Taxus and to determine the biological activity of ethanolic extracts from this plant. The objects of this study were the generative organs of Taxus canadensis, collected during the entire growing season (April–October) from plants growing in the Moscow region. The localization of various classes of polyphenols was determined by histochemical methods using light microscopy. Histochemical studies have shown the abundant presence of polyphenols in yew megastrobiles, microstrobiles, cones, seeds and aril. Ethanolic plant extracts were used to determine the biological activity. Flavans were dominant in the aril at various stages of vegetation, which was confirmed by our biochemical and histochemical studies. Extractive substances of T. canadensis show high antibacterial activity, especially in its shoot extracts. Ethanolic extracts from plant shoots showed greater biological activity than seed extracts. Aril extracts had the lowest cytotoxicity. Full article

Budding yeast Tiny Yeast Comet 1 (Tyc1) was previously identified based on homology to human p31^comet. The conserved homologous region is within the previously mapped p31^comet Taxol-stabilized microtubule binding domain at the C-terminus of p31^comet. The p31^comet protein mimics the 3-dimensional shape of the HORMA-domain protein Mitotic Arrest-Deficient 2 (Mad2). Several HORMA-domain proteins have been reported to form polymers. By employing negative staining electron microscopy, we observed that the Tyc1 protein forms comet-tail-shaped polymers in association with Taxol-stabilized microtubules. When associated with microtubules, Tyc1p polymers frequently displayed a braid-like appearance around and off the ends of the microtubules. Analysis of two mutant forms of Tyc1p revealed that the amino acid motifs that are conserved between Tyc1p and human p31^comet were essential for robust polymer formation. Tyc1p polymers that were formed in the presence of Mad2p in association with a Mad2-binding motif peptide were able to suppress Taxol-stabilized microtubule depolymerization that was induced by exposure to ice-cold CaCl₂. In conclusion, yeast Tyc1p forms polymers that can suppress Taxol-stabilized microtubule depolymerization, potentially yielding an insight into a microtubule-associated function for human p31^comet. Full article

Paclitaxel (Taxol), a taxane diterpenoid from Taxus species, is a clinically important microtubule-stabilizing anticancer agent widely used in chemotherapy. However, its supply remains limited by precursor scarcity and the molecule’s structural complexity. The biosynthetic pathway from geranylgeranyl diphosphate (GGPP) to paclitaxel is estimated to involve 19 to 23 enzymatic steps. Recent multi-omics approaches have substantially elucidated this pathway, yet key mechanistic questions persist, notably the formation of the oxetane ring. Complete heterologous biosynthesis is further hampered by poor cytochrome P450 (CYP) expression in non-native hosts and insufficient metabolic flux. This review synthesizes advances across four themes: (1) progressive elucidation of the biosynthetic pathway, with emphasis on the CYP-mediated oxygenation cascade and oxetane ring formation; (2) genomic and regulatory insights from Taxus genome assemblies, transcription factor networks, and spatial multi-omics; (3) metabolic engineering in microbial hosts, including Escherichia coli, Saccharomyces cerevisiae, and non-conventional chassis; and (4) plant-based heterologous production platforms. Critical bottlenecks are identified, including unresolved enzymatic steps, CYP functional expression, flux partitioning, and bioprocess scale-up. Strategies to overcome these challenges are discussed. Full article

Basic leucine zipper (bZIP) transcription factors are widely involved in plant growth, development, environmental adaptation, and secondary metabolism. However, the bZIP gene family in Taxus yunnanensis has not been systematically characterized, and its potential involvement in shading-responsive regulation of paclitaxel biosynthesis remains unclear. In this study, a genome-wide analysis was performed to identify and characterize the bZIP family in T. yunnanensis. Phylogenetic analysis, conserved motif and domain identification, promoter cis-element analysis, chromosomal localization, and expression profiling were conducted to investigate their structural features and regulatory potential. A total of 18 TyubZIP genes were identified and classified into 10 subfamilies. These genes exhibited variation in physicochemical properties but showed conserved structural features and nuclear localization. Promoter analysis revealed abundant light-responsive, hormone-related, and stress-related cis-elements. Expression profiling indicated tissue-specific expression patterns and diverse responses to shading treatment. WGCNA further identified candidate TyubZIP genes potentially associated with paclitaxel biosynthesis. Among them, TyuHY5 was selected for functional analysis. Subcellular localization and transcriptional assays demonstrated that TyuHY5 can bind to the promoter of TyuDBTNBT and positively regulate its activity. These findings provide the first genome-wide characterization of the bZIP family in T. yunnanensis and identify TyuHY5 as a shading-responsive candidate regulator of paclitaxel biosynthesis, providing insights that may inform the genetic improvement and cultivation strategies of Taxus for enhanced paclitaxel production. Full article

Medicinal plants have long served as a primary source of bioactive compounds with essential therapeutic applications. Recent advances in functional genomics and plant biotechnology now enable precise manipulation of metabolic pathways to enhance the production of specialized metabolites with medicinal value. However, an integrative understanding of how genomic discovery can be linked with pathway engineering, scalable production systems, and healthcare applications remains insufficiently developed. This knowledge gap limits the effective translation of molecular insights into the sustainable production of medicinally important compounds. The novelty of this review lies in its integrated framework linking functional genomic discovery with pathway engineering, synthetic biology, artificial intelligence-assisted prediction, and scalable production systems for medicinal plant-derived therapeutics. This review aims to provide a comprehensive overview of cutting-edge approaches in medicinal plant research, emphasizing high-throughput RNA sequencing, CRISPR/Cas9 gene editing, synthetic biology, and metabolic engineering for optimizing the production of key bioactive compounds, including artemisinin, cannabinoids, ginsenosides, and taxol. It further examines how these tools collectively support metabolite discovery, pathway elucidation, yield improvement, and biotechnological production in major medicinal plant systems. We explore the application of genomic and biotechnological approaches in plants such as Artemisia annua, Cannabis sativa, Panax ginseng, and Taxus baccata to enhance metabolite yields and promote sustainable production. The review highlights case studies that demonstrate how genetic modification, metabolic engineering, and synthetic pathway design have been successfully employed to increase the synthesis of key medicinal compounds. Moreover, we discuss the integration of artificial intelligence and machine learning to predict gene–metabolite relationships, support personalized phytochemical therapies, and facilitate sustainable, large-scale production. Finally, the review addresses the implications of these innovations for the pharmaceutical industry, healthcare, and agriculture, while also highlighting sustainable and scalable directions for future medicinal plant biotechnology. Full article

Breast cancer (BC) remains the most diagnosed malignancy among women worldwide, with approximately 2.3 million new cases and over 670,000 deaths reported annually. Resistance to conventional chemotherapeutic agents and treatment-related toxicity remain major challenges in BC management. Resveratrol, a naturally occurring polyphenol, has been proposed as a potential modulator of chemotherapy response; however, comparative evidence regarding its interaction with different classes of chemotherapeutic agents is limited. This study aimed to comparatively assess the effects of resveratrol on the cytotoxic, antiproliferative, and apoptotic responses induced by adriamycin, taxol, and cisplatin in MCF-7 BC cells. MCF-7 cells were treated with adriamycin, taxol, cisplatin, and resveratrol, either alone or in combination, across multiple concentrations for 24, 48, 72, and 96 h. Cell viability was evaluated using the trypan blue exclusion assay. Cellular proliferation was assessed via BrdU incorporation, while apoptosis and cell death profiles were analyzed using Annexin V staining and flow cytometry. Exposure to individual chemotherapeutic agents induced a significant time- and dose-dependent reduction in MCF-7 cell viability (p < 0.001). Resveratrol co-treatment further modulated chemotherapy-induced cytotoxicity in an agent- and time-dependent manner. Combination treatments markedly suppressed DNA synthesis compared with single-agent exposure (p < 0.01) and significantly increased apoptotic cell populations. Flow cytometric Annexin V/PI analysis demonstrated that early apoptotic cells ranged from 3.2–11.3% in single-agent treatments and increased to 0.04–50.4% in resveratrol-based combination groups. Similarly, late apoptotic/secondary necrotic cell fractions increased from 4.1–4.4% in single-agent treatments to 2.1–69.9% following combination therapy, indicating a substantially higher overall cell death response in selected treatment conditions. This study demonstrates that resveratrol modulates the cytotoxic and apoptotic responses of MCF-7 BC cells to adriamycin, taxol, and cisplatin in an agent- and time-dependent manner. The findings indicate that resveratrol acts as a context-dependent modulator of chemotherapy response. Although resveratrol generally enhanced cytotoxic and apoptotic responses in combination treatments, the magnitude of these effects varied depending on the chemotherapeutic agent and exposure conditions. Further preclinical and clinical studies are warranted to define their therapeutic relevance. Full article

The presence of aberrant double-stranded DNA (dsDNA) in the cytoplasm of cells is sensed by unique pattern recognition receptors (PRRs) to trigger innate immune response. The cyclic GMP–AMP synthase (cGAS)–stimulator of interferon genes (STING) signaling pathway is activated by the presence of non-self or mislocalized self-dsDNA from nucleus or mitochondria released in response to DNA damage or cellular stress in the cytoplasm. Activation of cGAS leads to the synthesis of the second messenger cyclic GMP–AMP (cGAMP), which binds and activates STING, triggering downstream signaling cascades that result in the production of type I interferons (IFNs) and proinflammatory cytokines. Here, we show that diverse immunostimulatory dsDNA ligands and chemotherapy agents like Doxorubicin and Taxol trigger the integrated stress response (ISR) by activating endoplasmic reticulum (ER) stress kinase, protein kinase RNA-like ER kinase (PERK), in addition to the canonical IFN pathways. PERK-mediated phosphorylation and inactivation of the alpha subunit of eukaryotic translation initiation factor-2 (eIF2α) result in the formation of stress granules (SGs). SG formation by dsDNA was significantly reduced in PERK knockout cells or by inhibiting PERK activity. Transcriptional induction of IFNβ and cytokines, ISR signaling, and SG formation by dsDNA was dampened in cells lacking PERK activity, STING, or key stress-granule nucleating protein, Ras-GAP SH3 domain-binding protein 1 (G3BP1), demonstrating an important role of the signal transduction pathway mediated by STING and SG assembly. Lastly, STING regulates reactive oxygen species (ROS) production in response to DNA damage, highlighting the crosstalk between DNA sensing and oxidative stress pathways. Together, our data identify STING–PERK–G3BP1 signaling axis that couples cytosolic DNA sensing to stress response pathways in maintaining cellular homeostasis. Full article

Background/Objectives: This pilot study investigates the feasibility of using patient-derived microtumors (PDMs) to assess chemotherapy response in epithelial ovarian cancer. Methods: Fresh tissue from 10 patients was used to develop PDMs, which were then tested against carboplatin/paclitaxel, carboplatin/docetaxel, and carboplatin/pegylated liposomal doxorubicin (PLD). Of the 10 PDMs, 3 were obtained from primary debulking surgery (PDS), and 7 were obtained at the time of interval debulking surgery following neoadjuvant chemotherapy. Results: When looking at PDMs derived from tissue collected at the time of PDS, we found that 100% of PDMs demonstrated a full response to carboplatin/PLD, while 30% showed a full response to all regimens, all of which were derived from high-grade serous carcinoma during PDS. The remaining PDMs showed moderate responses to carbo/taxol and carbo/doce. Conclusions: This study suggests that PDMs can be used to assess the efficacy of chemotherapy regimens, as a hypothesis-generating step toward future predictive validation. Full article

High-grade serous ovarian carcinoma is the most common and aggressive form of ovarian cancer, accounting for over 60% of cases and nearly 75% of deaths, mainly due to late diagnosis and tumor aggressiveness. Standard treatment is platinum-based chemotherapy with paclitaxel, but relapse is frequent. This study aimed to identify prognostic biomarkers for patients with poor survival outcomes after Taxol treatment using bioinformatics analysis. We examined the effects of TGFB2 mRNA expression and other markers on overall survival in serous ovarian cancer using the TCGA database, applying a multivariate Cox model that included interaction terms to identify TGFB2-dependent and independent prognostic markers, and controlling for age and treatment type. Candidate TGFB2-independent prognostic markers from TCGA were further validated using patient data from the KMplotter database. High TGFB2 mRNA expression emerged as a prognostic biomarker for three potential gene targets (TRPV4, STAU2, and HOXC4) associated with improved OS at low levels of gene target expression, we identified four additional markers (CLIC3, ANPEP/LAP1, RIN2, and EMP1) that exhibited a TGFB2-independent negative correlation between mRNA expression and OS across the full spectrum of gene expression values in the ovarian cancer cohort validated using independent dataset from KMplotter, for Taxol-treated ovarian cancer patients. This study proposes a panel of potential prognostic biomarkers for the treatment of ovarian cancer patients, particularly by leveraging TGFB2-dependent mRNA expression as a significant biomarker, alongside four additional TGFB2-independent prognostic markers, for patients undergoing Taxol-based therapies. Future prospective clinical trials will be required to validate these prognostic markers. Full article

Background/Objectives: Breast cancer is the most prevalent malignancy among women, and paclitaxel (PTX) is a first-line chemotherapeutic, but chemoresistance driven by ATP-binding cassette (ABC) transporters limits its efficacy. Single-target ABC inhibitors fail due to toxicity and cooperative transporter activity, creating an urgent need for safe multi-target strategies. Membrane cholesterol-rich lipid rafts support ABC transporter function, making cholesterol a key chemoresistance target. This study explored a cholesterol-targeted approach for overcoming PTX resistance. Methods: A PTX-resistant breast cancer line (MCF-7/PTX) showing ABCB1/ABCC3 co-upregulation and enriched cholesterol rafts was established. The effects of Polyphyllin H (PPH), a steroidal saponin from Paris polyphylla, were compared with lovastatin, a biosynthetic cholesterol inhibitor. In vitro and in vivo assays investigated Polyphyllin H’s cholesterol binding and effects on transporters, PTX accumulation, and tumor growth. Results: PPH directly binds membrane cholesterol, disrupting lipid rafts, downregulating ABCB1/ABCC3, reducing drug efflux, and increasing intracellular PTX to restore sensitivity. PPH showed superior cholesterol-binding and resistance-reversal efficacy than lovastatin, with faster, stronger PTX-enhanced cytotoxicity and tumor suppression. Conclusions: PPH reverses PTX resistance by targeting cholesterol-lipid rafts to inhibit multiple ABC transporters. This offers a safer adjuvant for PTX-based breast cancer therapy and a translational framework for other drug-resistant malignancies. Full article

Reprogramming of macrophages into the inflammatory state (also known as M1) is currently considered as an effective way of eliminating cancer cells, but systemic deployment of this strategy is likely to induce dangerous autoimmune reactions. Consequently, converting immunosuppressive M2-type macrophages into M1 systemically is not a safe and effective therapeutic approach against cancer. Through cleavable covalent linking of curcumin to the chemotherapeutic agent Paclitaxel (Taxol), we have created a novel prodrug (STO-1) that, upon intravenous delivery, selectively reprograms tumor-associated microglia and macrophages (TAMs) and eliminates glioblastoma (GBM) without triggering autoimmunity. Demonstrating its therapeutic efficacy, prolonged treatment of six orthotopic GBM-bearing mice with STO-1 resulted in 67% long-term survival, with three surviving mice exhibiting complete tumor clearance and one displaying minimal residual disease, as confirmed by high-resolution ex vivo T2-weighted MRI 85 days after tumor inoculation. In contrast, the vehicle-treated mice displayed extensive intracranial tumors with edema and hemorrhage. Mechanistically, scRNA-seq analysis indicated induction of multiple M1-associated transcripts (ccrl2, cxcl9, ccr2, ccl5) consistent with robust TAMs reprogramming. In striking contrast to the M2⟶M1 reprogramming of TAMs, M1-type macrophages were suppressed in the spleens of STO-1-treated cancer-free mice. Therefore, STO-1 induces selective anti-tumor immunity and GBM elimination without triggering systemic autoimmune reactions. Full article

Triple-negative breast cancers (TNBC) lack estrogen, progesterone, and express little, if any, HER2 receptors on their surface. No targeted therapies exist for this aggressive form of breast cancer. A library of enriched fractions from marine organisms was screened in a multi-parametric cytotoxicity assay using MDA-MB-231 and MDA-MB-468 TNBC cells, grown as spheroids (3D cultures). Spheroids better resemble tumors and are considered more clinically predictive. The assay measures apoptosis via the cleavage of caspase 3/7, viability via DNA content, and loss of membrane integrity via 7AAD staining at 24 h of treatment. Fractions were also tested in a traditional 2D MTT assay at 72 h. A fraction from the sponge Aplysina was active in the 3D assay. Aplysinamisine I was identified as the compound responsible for the activity. Aplysinamisine I induces apoptosis in MDA-MB-268 spheroids with an IC₅₀ of 2.9 ± 0.28 µM at 24 h. This novel activity is the most potent for the compound to date. Its IC₅₀ in the MTT assay at 72 h is >80 µM. Striking synergy with Taxol™ is shown in both cell lines. Proteomic analysis led to a differential protein expression profile. Through bioinformatics, this profile led to the hypothesis that the inhibition of nucleophosmin is the potential mode of action of the compound. However, initial studies show only a modest decrease in nucleophosmin expression in spheroids treated with aplysinamisine I. Full article

Pathogenic bacteria have developed different ways to cause infections. One strategy involves using components from host cells. This study looks at the role of the cytoskeleton in the human colon adenocarcinoma Caco-2 and neonatal non-transformed epithelial H4 cell lines during bacterial invasion. The bacteria studied include Cronobacter malonaticus, Cronobacter sakazakii, and E. coli K1, as they are associated with known diseases. Salmonella enteritidis 358 served as a positive control and E. coli K12 as a negative control for the invasion experiments. Before the invasion experiments, cell lines were treated with microfilament inhibitors, specifically Cytochalasin D, and microtubule inhibitors, such as Colchicine, Nocodazole, Vinblastine, and Taxol. The results showed that Cytochalasin D reduced about 60–80% of Cronobacter invasion into H4 cells and 50% of E. coli K1 invasion. In contrast, Colchicine reduced the invasion of some strains to just 2% compared to untreated cells. Meanwhile, Nocodazole and Taxol increased the invasion of C. sakazakii 709 and C. malonaticus 1569 into H4 cells by about 140% and 160%, respectively, while slightly inhibiting other strains. In Caco-2 cells, certain strains exhibited increased invasion due to Cytochalasin D, Vinblastine, and Colchicine treatment. This led to increases of up to 500%, 227%, and 248% compared to untreated cells. However, Nocodazole and Taxol decreased invasion into Caco-2 cells, with only E. coli K1 showing an increase of about 150% in Taxol-treated cells. The findings with eukaryotic cytoskeleton inhibitors on neonatal H4 cells suggest that bacterial invasion mainly relies on microfilaments or microfilament-dependent. No specific dependence on the cytoskeleton was seen in Caco-2 cells. In conclusion, cytoskeletal inhibitors significantly affected bacterial invasion, specifically Cronobacter, compared to untreated cells. This suggests that invasion methods may vary by strain and are influenced by how each inhibitor alters cytoskeleton behavior. Therefore, the invasion process, both with and without cytoskeletal inhibitors, is crucial for understanding how bacteria manipulate cell components during infection. Full article

Background/Objectives: Paclitaxel (PTX) is widely used in the treatment of a variety of solid tumours due to its broad-spectrum anti-tumour activity, but its use in brain gliomas is limited by insufficient blood–brain tumour barrier (BBTB) penetration and systemic toxicity. The aim of this study was to develop a Solutol HS-15-based micellar nanoparticle (PSM) to enhance the brain glioma targeting of PTX and reduce toxicity. Methods: PSMs were prepared by solvent injection and characterised for particle size, encapsulation rate, haemolysis rate and in vitro release properties. A C6 in situ glioma mouse model was used to assess the brain targeting and anti-tumour effects of the PSM by in vivo imaging, tissue homogenate fluorescence analysis and bioluminescence monitoring. Meanwhile, its safety was evaluated by weight monitoring, serum biochemical indexes and histopathological analysis. Results: The particle size of PSMs was 13.45 ± 0.70 nm, with an encapsulation rate of 96.39%, and it demonstrated excellent cellular uptake. In tumour-bearing mice, PSMs significantly enhanced brain tumour targeting with a brain drug concentration 5.94 times higher than that of free PTX. Compared with Taxol, PSMs significantly inhibited tumour growth (terminal luminescence intensity <1 × 10⁶ p/s/cm²/Sr) and did not cause significant liver or kidney toxicity or body weight loss. Conclusions: PSMs achieve an efficient accumulation of brain gliomas through passive targeting and EPR effects while significantly reducing the systemic toxicity of PTX. Its simple preparation process and excellent therapeutic efficacy support its use as a potential clinically translational candidate for glioma treatment. Full article