Search Results (48)

Bacterioruberin (BR), a C₅₀ carotenoid produced by halophilic archaea, is emerging as a bioactive molecule with potential anticancer relevance, but its activity in solid tumour and multidrug-resistant (MDR) models remains poorly defined. This in vitro study evaluated the cytotoxic, antiproliferative and growth-inhibitory effects of a chemically characterized bacterioruberin-rich carotenoid extract (BRCE) from Haloferax (H.) mediterranei in A549 lung adenocarcinoma, BT-549 triple-negative breast cancer and WM115 melanoma cells, as well as in paired sensitive/multidrug resistant (MDR) lung cancer models. Metabolic activity and proliferation were assessed by thiazolyl blue tetrazolium bromide (MTT) and carboxyfluorescein diacetate succinimidyl ester (CFDA-SE) assays, intracellular reactive oxygen species (ROS) by 2′,7′-dichlorodihydrofluorescein diacetate (H₂DCFDA) staining, and apoptosis-associated morphology by acridine orange/ethidium bromide (AO/EB) staining. Growth inhibition in A549/A549-CDR2 and NCI-H460/NCI-H460/R cells was analysed by sulforhodamine B (SRB) assay, while P-glycoprotein (P-gp) function and expression were examined using Rhodamine 123 (Rh123) accumulation and Western blotting. BRCE reduced metabolic activity and proliferation in a concentration- and time-dependent manner, increased intracellular ROS levels, and induced apoptosis-associated morphological changes in A549 cells. In MDR models, BRCE retained comparable growth-inhibitory activity in sensitive and resistant cells and partially attenuated P-gp-related drug efflux. These findings support further mechanistic investigation of BR in solid tumour and MDR cancer models. Full article

Colorectal cancer (CRC) remains one of the leading causes of cancer-related mortality worldwide, and the efficacy of conventional chemotherapy is frequently limited by systemic toxicity, chemoresistance, and tumor recurrence. Natural products derived from marine algae and plants have attracted increasing interest as multitarget adjuvant agents capable of modulating apoptosis, oxidative stress, and tumor-associated signaling pathways. In the present study, we evaluated the anticancer activity of commercially available formulations enriched in fucoxanthin, fucoidan, tocotrienols, astaxanthin, and apple polyphenols, either alone or in combination with doxorubicin (DOX), using two-dimensional and three-dimensional colorectal cancer models. Initial IC₅₀ screening in ovarian (OVCAR3), prostate (PC3), colorectal (Caco2 and HT-29), and non-tumorigenic colon epithelial cells demonstrated that formulations 2.1 and 10.0 exhibited the most relevant cytotoxic activity, particularly in colorectal cancer cells. Combined treatments with DOX significantly reduced cell viability compared to individual treatments, particularly in Caco2 cells, where viability decreased to approximately 10% under combined exposure conditions. Mechanistically, combined treatments enhanced caspase-3/7 activation in both Caco2 and HT-29 cells, indicating apoptosis-associated effects. These findings were further supported in three-dimensional spheroid models, where supplement combinations impaired spheroid expansion, induced apoptotic AO/EB staining patterns, and reduced HT-29 spheroid growth by approximately 30–35%, reaching inhibitory effects comparable to DOX alone. Collectively, these results suggest that plant- and algae-derived formulations enriched in antioxidant bioactives may enhance chemotherapy-associated antitumor responses through apoptosis-related mechanisms and modulation of tumor-like growth behavior. The present findings support the further exploration of natural-product-based adjuvant strategies in colorectal cancer therapy using more clinically representative chemotherapeutic schemes and in vivo models. Full article

Lung adenocarcinoma (LUAD) is the most common subtype of non-small cell lung cancer and remains a leading cause of cancer-related mortality worldwide. MicroRNAs (miRNAs) are critical regulators of tumor progression; however, the biological role and molecular mechanisms of miR-589-3p in LUAD remain unclear. In this study, the expression levels of miR-589-3p and WWC2 were analyzed using The Cancer Genome Atlas lung adenocarcinoma (TCGA-LUAD) datasets via the UALCAN platform. Flow cytometric apoptosis analysis and functional assays including CCK-8, colony formation, AO/EB staining, and Transwell invasion assays were performed in LUAD cell lines. The interaction between miR-589-3p and WWC2 was validated using dual-luciferase reporter assays, Western blotting, and rescue experiments. miR-589-3p expression was significantly elevated in LUAD tissues compared with normal lung tissues (p < 0.05) and was positively associated with an advanced tumor stage and lymph node metastasis (p < 0.05). Inhibition of miR-589-3p significantly suppressed proliferation and colony formation (p < 0.05), reduced invasive capacity (p < 0.05), and markedly increased apoptosis (p < 0.01) in LUAD cells. Dual-luciferase reporter assays confirmed WWC2 as a direct target of miR-589-3p, with miR-589-3p mimics significantly reducing WWC2 wild-type reporter activity (p < 0.05). WWC2 expression was significantly downregulated in LUAD tissues (p < 0.05), and WWC2 knockdown reversed the anti-proliferative, pro-apoptotic, and anti-invasive effects induced by miR-589-3p inhibition (p < 0.01). These findings demonstrate that miR-589-3p promotes lung adenocarcinoma progression by directly suppressing WWC2. The miR-589-3p/WWC2 axis represents a novel molecular mechanism contributing to LUAD malignancy and may provide a foundation for future mechanistic and translational studies. Full article

Human neuroglobin (Ngb) is a globin featuring a disulfide bond (Cys46–Cys55) and a redox-active cysteine residue (Cys120) and plays a dual role in cellular stress responses. In this study, we investigated how wild-type (WT) Ngb and its two mutants, C120S Ngb, in which Cys120 is replaced by serine, and A15C Ngb, which contains an engineered Cys15–Cys120 disulfide bridge, modulate oxidative stress in triple-negative breast cancer (MDAMB231) and hormone receptor-positive breast cancer (MCF-7) cells. In both cell lines, WT Ngb enhanced cell survival under H₂O₂-induced oxidative stress by scavenging reactive oxygen species (ROS) through oxidation of Cys120. In contrast, the C120S and A15C mutants lost this protective capacity and instead promoted apoptosis. Mass spectrometry analysis confirmed the oxidation of Cys120 to sulfenic acid in WT Ngb, whereas both mutants exhibited impaired redox activity, leading to elevated ROS levels, lipid peroxidation, and activation of caspase-9/3. AO/EB staining further revealed that WT Ngb attenuated DNA damage, while the mutants exacerbated apoptosis in both MDAMB231 and MCF-7 cells. These results demonstrate that Cys120 acts as a critical redox switch, dictating whether Ngb exerts cytoprotective or pro-apoptotic effects across different breast cancer cell types. Our findings suggest that WT Ngb may help protect normal tissues during cancer therapy, whereas engineered Ngb mutants could be used to selectively sensitize both triple-negative and hormone receptor-positive breast cancer cells to oxidative damage, offering a novel redox-targeted therapeutic strategy. Full article

Green nanotechnology offers a sustainable and eco-friendly approach for nanoframework synthesis. The present study intended to synthesize a novel eco-friendly encapsulated Zeolitic Imidazolate Framework-8 (ZIF-8) in a one-pot method using metabolites from the mangrove plant Conocarpus erectus (CE). Gas Chromatography–Mass Spectrometry (GC-MS) analysis of the extract revealed the presence of important bioactive metabolites. The synthesized material was evaluated by UV-Vis spectroscopy, X-ray diffraction (XRD), particle size analysis (PSA), zeta potential measurement, high-resolution transmission electron microscopy (HR-TEM), and Fourier transform infrared (FT-IR) spectroscopy studies. The environment-friendly mangrove metabolites aided by Zeolitic Imidazolate Framework-8 was found to be crystalline, rhombic dodecahedron structured, and size dispersed without agglomeration. The nanomaterial possessed a broad antimicrobial effect on drug-resistant microorganisms, including Candida krusei, Escherichia coli, Streptococcus Sp., Staphylococcus aureus, Enterococcus Sp., Pseudomonas aeruginosa, Klebsiella pneumoniae, C. propicalis, and C. albicans. Further, its cytotoxicity against MDA-MB-231 cells was found to be efficient. The morphological alterations exhibited by the antiproliferative impact on the breast cancer cell line were detected using DAPI and AO/EB staining. Therefore, ZIF-8 encapsulated mangrove metabolites could serve as an effective biomaterial with biomedical properties in the future. Full article

Gardenia jasminoides J.Ellis is an important medicinal and edible resource. The fruit of Gardenia jasminoides J.Ellis contains a natural iridoid called geniposide, which has the ability to dramatically suppress the growth of a number of cancer cell lines. This work examined the impact and potential mechanism of action of geniposide on oral squamous cell carcinoma using network pharmacology, molecular docking, molecular dynamics simulation, and cellular experiments. Based on network pharmacology, 145 potential targets of geniposide in the treatment of OSCC were found. The top five core targets were selected according to the degree values of the nodes, AKT1, EGFR, SRC, HSP90AA1, and PIK3R1, which involved signaling pathways and biological processes, such as the PI3K-Akt signaling pathway, pathways in cancer, phosphorylation, and the regulation of the apoptotic process. Molecular docking showed that geniposide exhibited good binding ability with the core targets AKT1 and EGFR. Molecular dynamics simulations further confirmed the stability of the binding between geniposide and the targets. The results of cell experiments showed that the activity of HSC-3 cells was dose-dependently inhibited by geniposide, and AO/EB staining showed that geniposide was able to induce programmed apoptosis. Meanwhile, it was found that the expressions of p-EGFR, p-AKT, and Bcl-2 were downregulated in HSC-3, and the expressions of PTEN, Bax, and Caspase-3 were upregulated. Geniposide may inhibit OSCC by affecting the PI3K-Akt signaling pathway and apoptotic process by regulating the expressions of p-EGFR, p-AKT, Bcl-2, Bax, Caspase-3, and PTEN. Full article

Lung adenocarcinoma is a prevalent, aggressive cancer with a poor prognosis due to early metastasis and resistance to treatment. LncRNA AFAP1-AS1 has been shown to be associated with the development of multiple carcinomas. This study investigates the functional role of AFAP1-AS1 in lung adenocarcinoma cell proliferation via miR-508-3p and ZWINT. Human lung adenocarcinoma A549 cells were transfected with siRNA constructs against AFAP1-AS1 (si-AFAP1-AS1) to silence its expression. Cell proliferation was evaluated via CCK-8 and colony-forming assays. Apoptosis was assessed using AO/EB staining, and invasion was determined via Transwell assay. The interaction between AFAP1-AS1, miR-508-3p, and ZWINT was confirmed via dual luciferase reporter assay and qRT-PCR analysis. Data were analysed using appropriate statistical tests. AFAP1-AS1 was significantly upregulated in lung adenocarcinoma cells compared to normal BEAS-2B cells. Silencing of AFAP1-AS1 resulted in a marked reduction in A549 cell proliferation and colony development, as observed in CCK-8 and colony formation assays. The AO/EB assay showed a significant increase in apoptosis (30 ± 4.4%) in si-AFAP1-AS1 transfected cells compared to control si-NC (3 ± 1.2%). In addition, knockdown of AFAP1-AS1 led to an upsurge of pro-apoptotic Bax and decline of anti-apoptotic Bcl-2 expression. The dual luciferase assay established the interaction between AFAP1-AS1 and miR-508-3p. Furthermore, ZWINT, identified as a target of miR-508-3p, was significantly upregulated in lung adenocarcinoma tissues. Overexpression of ZWINT rescued the inhibitory effects of AFAP1-AS1 silencing on cell proliferation, colony formation, and apoptosis, while also reversing the reduction in cell invasion. AFAP1-AS1 accelerates the development of lung adenocarcinoma by cell proliferation, apoptosis, and invasion via the miR-508-3p/ZWINT axis. Thus, targeting AFAP1-AS1 or its downstream regulatory axis could offer novel therapeutic approaches in lung adenocarcinoma treatment. Full article

Polymeric dielectrics have garnered significant interest worldwide due to their excellent comprehensive performance. However, developing polymeric dielectric films with high permittivity (ε_r) and breakdown strength (E_b) and low dielectric loss (tanδ) presents a huge challenge. In this study, amorphous aluminum oxide (Al₂O₃, AO) transition interfaces with nanoscale thickness were constructed between titanium oxide (TiO₂, TO) nanosheets and polyvinylidene fluoride (PVDF) to manufacture composites (PVDF/TO@AO). TO@AO nanosheets showed favorable dispersion in the polymer-based composites. Improved permittivity, suppressed dielectric loss, and enhanced breakdown strength were achieved by introducing AO coating with intermediate permittivity onto TO nanosheets to build a transition interface. The transition interface efficiently depressed the mobility of the charge carrier and electric conduction of the PVDF/TO@AO composites. As a result, the PVDF-based composite with 1 wt% TO@AO showed superior comprehensive performance, including high ε_r of ~12.7, low tanδ of ~0.017, and exceptional E_b of ~357 kV/mm. This strategy supplies a novel paradigm for the application of fabricating dielectric films with excellent comprehensive performance. Full article

To improve the potential of lupeol against cancer cells, a privileged structure, thiazolidinedione, was introduced into its C-3 hydroxy group with ester, piperazine-carbamate, or ethylenediamine as a linker, and three series of thiazolidinedione-conjugated compounds (6a–i, 9a–i, and 12a–i) were prepared. The target compounds were evaluated for their cytotoxic activities against human lung cancer A549, human breast cancer MCF-7, human hepatocarcinoma HepG2, and human hepatic LO2 cell lines, and the results revealed that most of the compounds displayed improved potency over lupeol. Compound 12i exhibited significant activity against the HepG2 cell line, with an IC₅₀ value of 4.40 μM, which is 9.9-fold more potent than lupeol (IC₅₀ = 43.62 μM). Mechanistic studies suggested that 12i could induce HepG2 cell apoptosis, as evidenced by AO/EB staining and annexin V-FITC/propidium iodide dual staining assays. Western blot analysis suggested that compound 12i can upregulate Bax expression, downregulate Bcl-2 expression, and activate the mitochondria-mediated apoptotic pathway. Collectively, compound 12i is worthy of further investigation to support the discovery of effective agents against cancer. Full article

Pseudomonas aeruginosa is an opportunistic pathogen that is especially dominant in people with cystic fibrosis; the drug resistance expressed by this pathogen and its capacity for adaptation poses a significant challenge to its treatment and control, thereby increasing morbidity and mortality rates globally. In this sense, the search for new treatment alternatives is imminent today, with products of plant origin being an excellent alternative for use. The objective of this research was to evaluate the antibacterial and antibiofilm potential and to explore the possible effect of ethanolic extracts from the wood and bark of Duguetia vallicola on the cell membrane. Microdilution assays showed the inhibition of bacterial growth by more than 50%, with the lowest concentration (62.5 μg/mL) of both extracts evaluated. Furthermore, we report the ability of both extracts to inhibit mature biofilms, with inhibition percentages between 48.4% and 93.7%. Intracellular material leakage experiments (260/280 nm), extracellular pH measurements, and fluorescence microscopy with acridine orange (AO) and ethidium bromide (EB) showed cell membrane damage. This indicates that the antibacterial action of ethanolic extracts of D. vallicola is associated with damage to the integrity of the cell membrane and consequent death of these pathogens. These results serve as a reference for future studies in establishing the mechanisms of action of these extracts. Full article

Liver fibrosis is the initial pathological process of many chronic liver diseases. Targeting hepatic stellate cell (HSC) activation is an available strategy for the therapy of liver fibrosis. We aimed to explore the anti-liver fibrosis activity and potential mechanism of phomopsterone B (PB) in human HSCs. The results showed that PB effectively attenuated the proliferation of TGF-β1-stimulated LX-2 cells in a concentration-dependent manner at doses of 1, 2, and 4 μM. Quantitative real-time PCR and Western blot assays displayed that PB significantly reduced the expression levels of α-SMA and collagen I/III. AO/EB and Hoechst33342 staining and flow cytometry assays exhibited that PB promoted the cells’ apoptosis. Meanwhile, PB diminished the number of autophagic vesicles and vacuolated structures, and the LC3B fluorescent spots indicated that PB could effectively inhibit the accretion of autophagosomes in LX-2 cells. Moreover, rapamycin and MHY1485 were utilized to further investigate the effect of mTOR in autophagy and apoptosis. The results demonstrated that PB regulated autophagy and apoptosis via the mTOR-dependent pathway in LX-2 cells. In summary, this is the first evidence that PB effectively alleviates liver fibrosis in TGF-β1-stimulated LX-2 cells, and PB may be a promising candidate for the prevention of liver fibrosis. Full article

Objective: The objective of this study was to examine the preparation process of DSPE-PEG-C60/NCTD micelles and assess the impact of fullerenol (C60)-modified micelles on the nephrotoxicity and antitumor activity of NCTD. Method: The micelles containing NCTD were prepared using the ultrasonic method and subsequently optimized and characterized. The cytotoxicity of micelles loaded with NCTD was assessed using the CCK-8 method on human hepatoma cell lines HepG2 and BEL-7402, as well as normal cell lines HK-2 and L02. Acridine orange/ethidium bromide (AO/EB) double staining and flow cytometry were employed to assess the impact of NCTD-loaded micelles on the apoptosis of the HK-2 cells and the HepG2 cells. Additionally, JC-1 fluorescence was utilized to quantify the alterations in mitochondrial membrane potential. The generation of reactive oxygen species (ROS) following micelle treatment was determined through 2′,7′-dichlorofluorescein diacetate (DCFDA) staining. Results: The particle size distribution of the DSPE-PEG-C60/NCTD micelles was determined to be 91.57 nm (PDI = 0.231). The zeta potential of the micelles was found to be −13.8 mV. The encapsulation efficiency was measured to be 91.9%. The in vitro release behavior of the micelles followed the Higuchi equation. Cellular experiments demonstrated a notable decrease in the toxicity of the C60-modified micelles against the HK-2 cells, accompanied by an augmented inhibitory effect on cancer cells. Compared to the free NCTD group, the DSPE-PEG-C60 micelles exhibited a decreased apoptosis rate (12%) for the HK-2 cell line, lower than the apoptosis rate observed in the NCTD group (36%) at an NCTD concentration of 75 μM. The rate of apoptosis in the HepG2 cells exhibited a significant increase (49%), surpassing the apoptosis rate observed in the NCTD group (24%) at a concentration of 150 μM NCTD. The HK-2 cells exhibited a reduction in intracellular ROS and an increase in mitochondrial membrane potential (ΔψM) upon exposure to C60-modified micelles compared to the NCTD group. Conclusions: The DSPE-PEG-C60/NCTD micelles, as prepared in this study, demonstrated the ability to decrease cytotoxicity and ROS levels in normal renal cells (HK-2) in vitro. Additionally, these micelles showed an enhanced antitumor activity against human hepatocellular carcinoma cells (HepG2, BEL-7402). Full article

Multicomponent reactions have emerged as an important approach for the synthesis of diverse and complicated chemical compounds. They have various advantages over two-component reactions, including the convenience of one-pot procedures and the ability to modify the structure of agents. Here, we employed in vitro and in silico studies to explore the anticancer potential of novel aminobenzylnaphthols derived from the Betti reaction (MMZ compounds). MTT assay was used to explore the cytotoxic activity of the compounds in pancreatic (BxPC-3 cells) and colorectal (HT-29) cancer cell lines or normal human lung fibroblasts (WI-38 cells). Proapoptotic properties of two derivatives MMZ-45AA and MMZ-140C were explored using AO/EB and annexin V-FITC/PI staining. In silico studies including ADMET profiling, molecular target prediction, docking, and dynamics were employed. The compounds exhibited cytotoxic properties and showed proapoptotic properties in respective IC₅₀ concentrations. As indicated by in silico investigations, anticancer activity of MMZs can be attributed to the inhibition of ADORA1, CDK2, and TRIM24. Furthermore, compounds exhibited favorable ADMET properties. MMZs constitute an interesting scaffold for the potential development of new anticancer agents. Full article

Clinical trials of new drugs often face a high failure rate of approximately 45 percent due to safety and toxicity concerns. Repurposing drugs with well-established safety profiles becomes crucial in addressing this challenge. Colon cancer ranks as the third most prevalent cancer and the second leading cause of cancer related mortality worldwide. This study focuses on the RNA-binding protein pumilio1 (PUM1), a member of the PUF family involved in post-transcriptional gene expression regulation. By utilizing molecular docking techniques and FDA-approved drugs, potential inhibitors against PUM1 were identified. Notably, dolasetron and ketoprofen demonstrated promising results, exhibiting strong binding affinity, hydrophobic interactions, and favorable chemical reactivity according to Conceptual-DFT calculations. Both compounds effectively reduced cell viability, with IC50 values of 150 µM and 175 µM, respectively and shows long term inhibitory effects as seen by reduced in number of colonies. Moreover, they exhibited inhibitory effects on colon cancer stem cells, as indicated by reduced colonospheroid size and numbers. Apoptosis is induced by these compounds and has triggered activation of executioner caspase 3/7 in HCT116 cells which is evident through a caspase 3/7 assay and AO/EB staining, while the non-toxic effect of these compounds was evident from viability against non-cancerous cell line and hemolysis assay. Additionally, the treatment group showed a significant decrease in PUM1 and cancer stem cell markers expression compared to the control group. In conclusion, this study highlights the potential of targeting PUM1 as a novel approach to colon cancer treatment. Dolasetron and ketoprofen demonstrate promise as effective anti-cancer and anti-cancer stem cell drugs, inducing apoptosis in colon cancer cells through inhibition of PUM1. Full article

Breast cancer is among the most recurrent malignancies, and its prevalence is rising. With only a few treatment options available, there is an immediate need to search for better alternatives. In this regard, nanotechnology has been applied to develop potential chemotherapeutic techniques, particularly for cancer therapy. Specifically, albumin-based nanoparticles are a developing platform for the administration of diverse chemotherapy drugs owing to their biocompatibility and non-toxicity. Visnagin, a naturally derived furanochromone, treats cancers, epilepsy, angina, coughs, and inflammatory illnesses. In the current study, the synthesis and characterization of albumin visnagin (AV) nanoparticles (NPs) using a variety of techniques such as transmission electron microscopy, UV-visible, Fourier transform infrared, energy dispersive X-ray composition analysis, field emission scanning electron microscopy, photoluminescence, X-Ray diffraction, and dynamic light scattering analyses have been carried out. The MTT test, dual AO/EB, DCFH-DA, Annexin-V-FITC/PI, Propidium iodide staining techniques as well as analysis of apoptotic proteins, antioxidant enzymes, and PI3K/Akt/mTOR signaling analysis was performed to examine the NPs’ efficacy to suppress MDA-MB-468 cell lines. The NPs decreased cell viability increased the amount of ROS in the cells, disrupted membrane integrity, decreased the level of antioxidant enzymes, induced cell cycle arrest, and activated the PI3K/Akt/mTOR signaling cascade, ultimately leading to cell death. Thus, AV NPs possesses huge potential to be employed as a strong anticancer therapy alternative. Full article