Search Results (590)

The increasing prevalence of cancer necessitates the development of novel and effective therapeutic agents. This study evaluates the anticancer potential of biosynthesized copper oxide nanoparticles (CuO NPs) using Camellia sinensis extract against human colon and breast cancer cells. The CuO NPs were characterized using various techniques to confirm their structure, size, morphology, and functional groups. The average size of CuO NPs synthesized was 20–60 nm, with spherical shape. The cytotoxic effects of these CuO NPs reveal a dose-dependent reduction in cell viability with 50% inhibitory concentration (IC₅₀) at 58.53 ± 0.13 and 53.95 ± 1.1 μg/mL, respectively. Further investigation into the mechanism of action was conducted using flow cytometry and apoptosis assays, which indicated that CuO NPs induced cell cycle arrest and apoptosis in cancer cells. Reactive oxygen species (ROS) generation, caspase activity assay, and comet assay were also performed to elucidate the underlying pathways, suggesting that oxidative stress and DNA damage play pivotal roles in the cytotoxicity observed. Overall, our findings demonstrate that biosynthesized CuO NPs exhibit notable anticancer activity against colon and breast cancer cells, with moderate selectivity over normal cells, highlighting their potential as a therapeutic agent due to their biocompatibility. However, further studies are required to validate their selectivity and safety profile. Full article

Euphorbia hirta L. is traditionally used to treat tumors and has demonstrated anticancer effects. This study evaluated the phytochemical composition, toxicity, and antitumor activity of saline extract (SE) from E. hirta leaves in mice. Phytochemical analysis included thin layer chromatography, high-performance liquid chromatography, and quantification of phenols, flavonoids, and proteins. Acute toxicity (2000 mg/kg) assessed mortality, hematological, biochemical, histological parameters, water/feed intake, and body weight. Genotoxicity was evaluated via comet and micronucleus assays. Antitumor activity was tested in vitro and in vivo on sarcoma 180. SE contained 107.3 mg GAE/g phenolics and 22.9 mg QE/g flavonoids; the presence of gallic and ellagic acids was detected. Protein concentration was 12.16 mg/mL with lectin activity present. No mortality, organ damage, or genotoxic effects occurred in toxicity tests. SE demonstrated in vitro cytotoxicity against sarcoma cells (IC₅₀: 10 µg/mL). In vivo, SE (50–200 mg/kg) reduced tumor weight by 70.2–72.3%. SE modulated IL-2, IL-4, IL-6, IL-17, IFN-γ, and TNF-α in tumor environment. Tumors showed inflammatory infiltrate, necrosis, and fibrosis after treatment. These findings position the extract as a promising candidate for further development as a safe, plant-based antitumor agent. Full article

Background/Objectives: Colorectal cancer (CRC) is among the most prevalent malignant neoplasms globally. Chemotherapeutic treatment strategies have demonstrated minimal improvement over the past decade. Combination therapies, including those with nutraceuticals, are currently being investigated as promising alternatives to enhance therapeutic efficacy. The organosulfur garlic extract diallyl disulfide (DADS) has demonstrated anti-tumoral activity in several types of cancer. This study aimed to investigate the effects of DADS and 5-fluorouracil (5-FU), both individually and in combination, on the human CRC cell lines Caco-2 and HT-29. Methods: Caco-2, HT-29, and non-tumoral human umbilical vein endothelial cells (HUVEC) were exposed to DADS (25–600 µM) and 5-FU (5–100 µM), either individually or in simultaneous combination (DADS 100 µM + 5-FU 100 µM), for 24 h. Cytotoxicity was evaluated in all three cell lines. In addition, the effects of these treatments on oxidative stress, cell migration, genotoxicity, cell death, global DNA methylation, and gene–nutraceutical interactions were assessed in both tumor cell lines. Results: DADS demonstrated cytotoxic effects at high concentrations in Caco-2, HT-29, and HUVECs and induced DNA damage in both colorectal cancer cell lines. The combination of DADS and 5-FU significantly promoted apoptotic cell death, increased genotoxicity, elevated global DNA methylation, and inhibited cell migration, with these effects being particularly pronounced in HT-29 cells. Conclusions: We provide evidence that DADS combined with 5-FU is potentially useful in the therapy of CRC. However the combination of nutraceuticals and chemotherapy must consider the distinct molecular and phenotypic characteristics of each tumor cell line. Full article

Background/Objectives: Thymus longicaulis subsp. chaubardii (TL) (Rchb.f.) Jalas is widely used in traditional Turkish medicine for respiratory, digestive and uro-genital disorders. The aim of this study was to determine its phytochemical profile and to evaluate its cytotoxic, genotoxic and acute oral toxicity effects. Methods: The phenolic composition of the methanolic extract was determined by HPLC-DAD. Cytotoxicity and genotoxicity were evaluated in NIH3T3 cells using MTT, comet and micronucleus assays. Acute toxicity was evaluated in rats at doses of 300 and 2000 mg/kg body weight according to the OECD Guideline 420. Results: Rosmarinic acid (87.37 ± 5.39 µg/mg) was the major phenolic compound. TL extract showed >90% cell viability at 50–200 µg/mL, indicating no cytotoxicity. Comet assay revealed a slight increase in DNA damage at 100–200 µg/mL (p < 0.001), though significantly lower than the H₂O₂ group (p < 0.001). No significant (p > 0.05) effect was observed in the micronucleus assay between the treated groups. In rats, TL extract caused no mortality or behavioral changes over 14 days. No significant differences were observed in body or organ weights. Hematologically, platelet count increased (p < 0.001) and eosinophils decreased (p < 0.01 and p < 0.001). Biochemical tests showed lower ALT and AST levels (p < 0.01 and p < 0.05, respectively) and significantly decreased triglycerides in the high-dose group (p < 0.001). Histopathological examination showed no organ damage. Conclusions: The results of this study indicate that TL methanol extract is non-toxic up to 2000 mg/kg and exhibits no significant cytotoxic or genotoxic effects. These findings support its safe use and traditional medicinal value. Full article

In the environment, plastic waste degrades into small particles known as microplastics and nanoplastics (MNPLs), depending on their size. Given the potential harmful effects associated with MNPL exposure, it is crucial to develop environmentally representative particles for hazard assessment. These so-called true-to-life MNPLs are generated through in-house degradation of real-world plastic products. In this study, we produced titanium-doped nanoplastics (NPLs) from opaque polyethylene terephthalate (PET) milk bottles, which contain titanium dioxide as a filler. The resulting PET(Ti)-NPLs were thoroughly characterized using scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), mass spectrometry (MS), dynamic light scattering (DLS), ζ-potential measurements, transmission electron microscopy (TEM), and Fourier-transform infrared (FTIR) spectroscopy. Human-derived THP-1 monocytes were employed to investigate particle uptake kinetics, dosimetry, and genotoxicity. A combination of flow cytometry and inductively coupled plasma mass spectrometry (ICP-MS) enabled the quantification of internalized particles, while the comet assay assessed DNA damage. The results revealed dose- and time-dependent effects of PET(Ti)-NPLs on THP-1 cells, particularly in terms of internalization. Titanium doping facilitated detection and influenced genotoxic outcomes. This study demonstrates the relevance of using environmentally representative nanoplastic models for evaluating human health risks and underscores the importance of further mechanistic research. Full article

Background/Objectives: Natural products are important in healthcare due to their accessibility and linkage to a healthy lifestyle. However, their effectiveness is uncertain due to insufficient scientific data. Cancer patients are frequent users of natural products to relieve symptoms or for chemoprevention. Eugenia uniflora leaf essential oil (EO), traditionally used for digestive disorders, emerges as a potential antineoplastic agent. We investigated the cytotoxic and antiproliferative effects of E. uniflora EO in human normal CCD 841 CoN and tumoral Caco-2 colonic cell lines. Methods: CCD 841 CoN and Caco-2 cells were exposed to different concentrations of E. uniflora EO, and the cytotoxicity was determined by MTT and Trypan Blue assays. Cell proliferation kinetics were analyzed at a low EO concentration, and the induction of DNA damage and oxidative stress was assessed by Comet and Cellular ROS assays. Results: Both cell lines exhibited cytotoxicity produced by the EO and decreased cell viability of the exposed cells and their progeny. CCD 841 CoN proliferation was impaired by low EO concentration, while the proliferation kinetics of the Caco-2 cells was modified. EO treatment induced variable DNA damage and oxidative stress depending on the cell line. Conclusions: Our results suggest that E. uniflora EO may prevent the proliferation of normal cells, inducing loss of viability. The EO produced cytotoxic and antiproliferative effects in tumoral cells by inducing DNA damage and increased oxidative stress. These effects support the consideration of E. uniflora EO (or its bioactive compounds) as a potential agent for the chemoprevention and treatment of colorectal cancer. Full article

The study of the effects of 2.45 GHz electromagnetic fields on the health and safety of people and organisms as a whole is essential due to their widespread use in everyday life. It is known that they can cause thermal and non-thermal effects—at the molecular, cellular and organismal level. Yeast suspensions were treated with 2.45 GHz microwave radiation in the near-field of antenna at two distances (2 and 4 cm) and two time periods (20 and 60 min)—setups resembling the use of mobile devices. The release of UV-absorbing substances from the cells was studied as an indicator of membrane permeabilization, total intracellular antioxidant activity and reduced glutathione were determined, and a comet assay for damage to the DNA was performed. A correlation between reduced antioxidants and increased membrane permeability during EMF treatment was observed at a distance of 2 cm for 20 min, suggesting the presence of oxidative stress, while a similar effect was not observed with conventional heating. Slightly increased membrane permeability was observed after irradiation for 60 min at a distance of 4 cm, but this was not related to the antioxidant status of the cells. A trend towards increased DNA damage was observed under both conditions. Full article

Ecuador, located in South America, ranks among the countries with the highest rates of pesticide use per unit of cropland. Pesticide exposure is linked to genotoxic effects and carcinogenicity. While most studies evaluating the effects of pesticides focus on the active ingredient, commercial formulations are complex mixtures of several components that may alter their toxicological profile. In this study, we analyzed four pesticides commonly used in corn cultivation, and their typical field mixtures, including the herbicides atrazine and pendimethalin, the insecticides chlorpyrifos and cypermethrin, and a fertilizer, to evaluate their genotoxic effects, oxidative status, and potential to induce cellular transformation. CHO-K1 cells were treated with subtoxic doses of these formulations. MTS, comet, micronucleus, H2AX expression, SOD and GPx activity, and wound healing assays were performed. The results showed these formulations induced genotoxicity, evidenced by the comet assay. Additionally, exposure activated cellular DNA repair mechanisms, evidenced by a 1.89- to 2.63-fold increase in H2AX expression across all treatments and mixtures after 10 h. Notably, pendimethalin was associated with signs of cellular transformation, as evidenced by a 1.4-times greater cell migration observed in the wound healing assay. These findings suggest that even at subtoxic concentrations, these pesticide formulations can cause genetic damage and potentially alter cellular control mechanisms. Full article

Background/Objectives: Fruits and vegetables (F&Vs) are major dietary sources of phytochemicals, crucial for preventing non-communicable diseases. However, barriers such as preparation inconvenience and a short shelf life hinder their consumption. F&V-coated foods have emerged as an alternative. This human nutrition intervention study assessed the effects of a blended F&Vs mixture versus an F&V-coated food on phytochemical absorption and chronic disease risk markers. It also explored how genetic variation influences physiological responses to these F&V products. Methods: In this randomized-controlled trial, participants were assigned to one of three dietary interventions: a blended F&V mixture (“F&V Blend”), a rice-based cereal product coated with this blend (“Coated Pearl”), or the same product without the F&V mixture (“Uncoated Pearl”). The four-week study included a two-week run-in and a two-week intervention phase, each followed by a test day. Measurements included DNA damage resistance (comet assay), plasma antioxidant status (Trolox capacity and superoxide levels), microvasculature health (retinal analysis), and plasma phytochemical concentrations (colorimetric analyses or HPLC). To assess group differences, a linear mixed model was used. Fifteen polymorphic genes related to phytochemical metabolism and oxidative stress were tested using TaqMan and PCR, with outcomes analyzed via ANOVA. Results: The F&V Blend and Coated Pearl products increased plasma carotenoid levels versus the Uncoated Pearl product. Only the F&V Blend improved retinal dilation and DNA resistance. Surprisingly, the Uncoated Pearl product enhanced antioxidant capacity, lowered superoxide levels, and improved retinal microvasculature. Genotype effects were minimal, except for HNF1A, where wildtypes in the Uncoated Pearl group showed a higher antioxidant capacity. Conclusions: Fresh F&Vs were more effective than coated alternatives in improving vascular health and DNA protection. Full article

In this study, the chemopreventive effects of rosmarinic acid (RA), a major phenolic acid of the plant Rosmarinus officinalis L., against the carcinogenic naturally occurring mycotoxin aflatoxin B1 (AFB1) were investigated using both in silico and in vitro approaches. The in silico investigation of the chemical reactions between rosmarinic acid and the carcinogenic metabolite of AFB1, aflatoxin B1 exo-8,9-epoxide (AFBO), was conducted by activation free energies calculations with DFT functionals M11-L and MN12-L, in conjunction with the 6-311++G(d,p) flexible basis set and implicit solvation model density (SMD), according to a newly developed quantum mechanics-based protocol for the evaluation of carcinogen scavenging activity (QM-CSA). Following the computational analyses, the chemoprotective effects of RA were further studied in vitro in human hepatocellular carcinoma HepG2 cells by analyzing its influence on AFB1-induced genotoxicity using a comet assay, γH2AX, and p-H3, while its impact on cell proliferation and cell cycle modulation was assessed using flow cytometry. Our computational results revealed that the activation free energy required for the reaction of RA with AFBO (14.86 kcal/mol) is significantly lower than the activation free energy for the competing reaction of AFBO with guanine (16.88 kcal/mol), which indicates that RA acts as an efficient natural scavenger of AFBO, potentially preventing AFB1-specific DNA adduct formation. The chemoprotective activity of RA was confirmed through in vitro experiments, which demonstrated a statistically significant (p < 0.05) reduction in AFB1-induced single- and double-strand breaks in HepG2 cells exposed to a mixture of AFB1 and RA at non-cytotoxic concentrations. In addition, RA reversed the AFB1-induced reduction in cell proliferation. Full article

Background: This study aimed to evaluate the therapeutic efficacy of intravesical tigecycline administration in a rat model of cystitis induced by a tigecycline-sensitive, extensively drug-resistant (XDR) Acinetobacter baumannii strain. Methods: Thirty-six female Wistar albino rats were inoculated intravesically with XDR A. baumannii to induce cystitis. Twenty-four rats that developed infection were divided into four groups: untreated control, saline irrigation, low-dose tigecycline (6.25 mg/kg), and high-dose tigecycline (25 mg/kg). Microbiological clearance was assessed via urine cultures on days 3 and 5. Bladder tissues were analyzed histopathologically and for genotoxicity using the Comet assay. Results: On day 5, microbiological clearance was significantly higher in tigecycline-treated groups compared to controls (p = 0.028). Histopathology revealed significantly more inflammation in the high-dose tigecycline group (p = 0.029). Genotoxicity was observed in both tigecycline groups, independent of dose (p < 0.05). Conclusions: Intravesical tigecycline demonstrated microbiological efficacy against XDR A. baumannii-induced cystitis. However, its inflammatory and genotoxic potential necessitates further preclinical evaluation. Full article

Oxidative stress (OS) contributes to poor sperm parameters and increased sperm DNA fragmentation (sDF), yet effective therapeutic strategies remain limited. This study aimed to evaluate the in vitro efficacy of pentoxifylline (PTX) in improving sperm motility and reducing OS and sDF in men with isolated asthenozoospermia. Thirty semen samples from patients with asthenozoospermia were processed using density gradient centrifugation. Each sample was divided into two aliquots: one treated with PTX at a dose of 3.6 mM and the other without PTX treatment. The sperm viability and motility were assessed at 30 min, 1 h, 2 h, and 24 h post-treatment. OS was evaluated using nitro blue tetrazolium staining and a chemiluminescence assay. sDF was assessed using the alkaline Comet assay. The sperm samples treated with PTX, compared to the controls, exhibited a significant increase in total sperm motility (71.8 ± 23.03% versus 47.47 ± 4.88%, respectively; p < 0.0001). However, no significant difference was observed in the sperm viability. PTX treatment significantly reduced ROS production and sDF levels compared to controls (p < 0.01). These findings suggest that in vitro PTX supplementation enhances sperm motility and reduces the nuclear sperm injury associated with seminal ROS production. Therefore, PTX supplementation in vitro may be beneficial in assisted reproductive technology procedures involving men with asthenozoospermia. Full article

Nanotechnology offers alternative approaches to the discovery of anticancer drugs. Hydrophobic bioactive components can be included in the cores of amphiphilic nanocarriers, which leads to the formation of a water-dispersible product with improved bioavailability, facilitated excretion, and reduced systemic toxicity in the treated organisms. This study was aimed at the formation of polymer nanocarriers, loaded with anticancer drug precursor podophylotoxin (PPT) or PPT-containing juniper leaf extracts, seeking to study their antineoplastic activity in A-431 epidermoid carcinoma cells and HaCaT normal keratinocytes. The amphiphilic, biodegradable, and biocompatible MPEG-b-PLA diblock copolymer was self-assembled in aqueous media into nanosized particles, whose physicochemical characteristics were studied by dynamic light scattering, transmission electron microscopy, and other methods. High encapsulation efficiency was determined for the PPT component-loaded micelles. DNA fragmentation, cell cycle arrest, nuclear condensation, membrane lipid order assessment, reactive oxygen species, and apoptosis induction by the loaded nanocarriers in A-431 or HaCaT cells were analyzed by the comet assay, FACS, Hoechst DNA staining, Laurdan generalized polarization, and other methods. As a result of various cellular processes induced by the PPT component-loaded nanoparticles, effector caspase-3 and caspase-7 activation showed selectivity towards tumor cells compared to the normal cells. The newly obtained PPT-containing nanoparticles have applications as potential drugs in the prospective nanomedicine. Full article

Cr(III) and Co(II) can be potentially toxic to cells and induce a number of morphological and biochemical changes. These metals are widely used in many industries and can cause environmental pollution. They are the components of dietary supplements, vitamin and mineral products, and energy drinks. Moreover, these metals are used in dentistry and orthopedics as components of implants. Data about the mechanism of genotoxic effects of Cr(III) and Co(II) are still incomplete. The aim of this study was to analyze the genotoxic effects of chromium(III) and cobalt(II) and their mixtures on two cell lines: mouse embryo fibroblast cell line BALB/3T3 and human hepatocellular carcinoma cell line G2 (HepG2). The BALB/3T3 and HepG2 cell lines were exposed to chromium chloride and cobalt chloride at concentrations ranging from 100 to 1400 µM. The genotoxicity assays used were the comet and micronucleus assays. On the basis of the results obtained from the first stage of the research, the concentrations of elements were selected in order to determine the interactions between them. The tested cell lines were treated with mixtures of the following compounds: chromium chloride at the concentration of 200 μM and cobalt chloride at the concentration of 1000 μM or chromium chloride at the concentration of 1000 μM and cobalt chloride at the concentration of 200 μM in the genotoxicity assays. This study shows that both cobalt(II) and chromium(III) cause genotoxic effects in the BALB/3T3 and HepG2 cell lines. A statistically significant increase in the percentage of comets was observed with increasing concentrations of Co(II) and Cr(III) compared to the control. A statistically significant induction of chromosomal aberrations was also observed in the micronucleus test. Moreover, chromium(III) at a concentration of 200 µM had a protective effect against the toxic concentration of cobalt(II) at a concentration of 1000 µM. The toxic effect of cobalt chloride and chromium chloride was confirmed in this study. Further research is needed on the genotoxic effects of cobalt(II) and chromium(III), especially due to the growing popularity of dietary supplements containing compounds of these metals and doubts as to the safety of their use. Full article

Multiple sclerosis (MS) is a neuroinflammatory disease where oxidative stress and DNA damage may influence disease progression. We investigated whether defects in base excision repair (BER) pathways contribute to MS by combining functional DNA repair assays, gene expression profiling, and genotype analysis. We collected peripheral blood mononuclear cells from 70 MS patients and 61 healthy controls. These cells were subjected to tert-butyl hydroperoxide (TBH)-induced oxidative stress, and comet assay kinetics were measured over a period of 60 min. Additionally, we quantified the mRNA expression of nine key BER genes and genotyped selected polymorphisms related to DNA repair capacity. Samples from MS patients exhibited significantly higher levels of TBH-induced DNA lesions and displayed a distinct repair trajectory over time, as indicated by area-under-the-curve (AUC) analyses (p < 0.001). The transcripts of MBD4 and NTHL1 were notably reduced in MS patients compared to those in the controls (p < 0.0001). A logistic regression analysis revealed an association between the specific BER-related single nucleotide polymorphisms (SNPs) rs3087404, rs4135054, and rs1052133 and ineffective DNA repair. Subset analyses of B cells, CD4⁺ cells, and CD8⁺ cells further supported the presence of altered repair kinetics in MS, even though some subsets exhibited similar baseline lesion levels. Our findings suggest that impaired oxidative DNA repair is present in MS, likely driven by functional deficits in repair kinetics and alterations in the expression of BER genes and polymorphisms. This integrated approach highlights DNA repair pathways as potential therapeutic or prognostic targets in MS. Full article