Mucilage-assisted fabrication of molybdenum trioxide nanostructures for photothermal ablation of breast cancer cells.

Nanostructures have been used for various biomedical applications due to their optical, antibacterial, magnetic, antioxidant, and biocompatible properties. Cancer is a prevalent disease that severely threatens human life and health. Thus, innovative and effective therapeutic approaches are urgently required for cancer. Photothermal therapy (PTT) is a promising approach to killing cancer cells. In this investigation, we developed a low-cost, simple, green technique to fabricate molybdenum trioxide nanostructures (MNs) using Opuntia ficus-indica mucilage as a template. Moreover, the MNs were functionalized with folic acid (FA) for cancer PTT. The X-ray diffractometer results revealed that the prepared MNs have an orthorhombic crystal phase. The transmission electron microscope image of MNs shows a flake shape with 20-150 nm diameter. The cytotoxicity of MNs and FA-conjugated MNs was studied in vitro. These cell viability assay results suggested that fabricated MoO3 nanostructures reduced 25% of cell viability in MCF-7 cells, even at high doses. However, even with high-dose treatment, FA/MNs do not cause significant cell death. Acridine orange/ethidium bromide (AO/EB) staining revealed DNA and chromatin condensation in MCF-7 cells exposed to MNs. Overall, the in vitro study results suggested that FA/MNs have excellent biocompatibility, which applies to biomedical applications. MNs dispersion temperature gradually increases from 26 to 58°C under 808 nm laser irradiation. We found significant mortality rates after NIR irradiation in MNs- or FA/MNs-treated MCF-7 cells. These findings suggest that FA/MNs can be used as an effective photothermal agent to treat breast cancer.

Maillard Reaction-Derived S-Doped Carbon Dots Promotes Downregulation of PPARγ, C/EBPα, and SREBP-1 Genes In-Vitro.

Carbon nanodots (CDs) are commonly found in food products and have attracted significant attention from food scientists. There is a high probability of CD exposure in humans, but its impacts on health are unclear. Therefore, health effects associated with CD consumption should be investigated. In this study, we attempted to create a model system of the Maillard reaction between cystine and glucose using a simple cooking approach. The CDs (CG-CDs) were isolated from cystine-glucose-based Maillard reaction products and characterized using fluorescence spectroscopy, X-ray diffractometer (XRD), and transmission electron microscope (TEM). Furthermore, human mesenchymal stem cells (hMCs) were used as a model to unravel the CDs' cytotoxic properties. The physiochemical assessment revealed that CG-CDs emit excitation-dependent fluorescence and possess a circular shape with sizes ranging from 2 to 13 nm. CG-CDs are predominantly composed of carbon, oxygen, and sulfur. The results of the cytotoxicity evaluation indicate good biocompatibility, where no severe toxicity was observed in hMCs up to 400 µg/mL. The DPPH assay demonstrated that CDs exert potent antioxidant abilities. The qPCR analysis revealed that CDs promote the downregulation of the key regulatory genes, PPARγ, C/EBPα, SREBP-1, and HMGCR, coupled with the upregulation of anti-inflammatory genes. Our findings suggested that, along with their excellent biocompatibility, CG-CDs may offer positive health outcomes by modulating critical genes involved in lipogenesis, homeostasis, and obesity pathogenesis.

Fabrication of myristic acid-potato starch complex nanostructures and assessment of their cytotoxic behavior.

BACKGROUND: Lipids and carbohydrates perform essential functions in foods. In recent decades, food scientists have studied the effects of carbohydrate-lipid interactions on the functional properties of food. However, the ways in which carbohydrate-lipid complex-derived materials affect the biological system are unknown. In this study, a myristic acid-potato starch complex was created using a simple cooking approach. The complex was employed as a precursor for the fabrication of myristic acid-potato starch complex-based nanostructured materials (MPS-NMs) through a liquid-liquid extraction approach. A study was conducted on the structural and cytotoxic features of the fabricated MPS-NMs. RESULTS: Transmission electron microscopy images confirmed the formation of spherical nanostructures, 3-60 nm in size. After 24 h exposure, the chloroform fraction-based and n-hexane fraction-based MPS-NMs increased cell death by ~90% and ~ 82%, respectively. Chloroform fraction-based MPS-NMs (CMPS-NMs) triggers apoptotic cell death in human mesenchymal stem cells (hMSCs). n-Hexane fraction-based MPS-NMs (HMPS-NMs) treated cells have red color-intact nuclei, attributed to necrotic cell death. The CMPS-NMs and HMPS-NMs significantly decreased the mitochondria membrane potential and increased the intracellular reactive oxygen species (ROS) levels. We observed significant downregulation in flavin-containing monooxygenase (FMO), Ataxia Telangiectasia Mutated (ATM), and uridine diphosphate glucuronosyltransferases (UGT) gene expression levels in the exposed cells of CMPS-NMs and HMPS- NMs. In addition, we found upregulation of glutathione-disulfide reductase (GSR) and glutathione S-transferase A4 (GSTA4) genes in CMPS-NMs, and HMPS-NMs exposure. CONCLUSION: The cooking process may lead to the formation of nanostructured material in food systems. Chloroform fraction-based MPS-NMs and HMPS-NMs may contribute to cell metabolic disorders. © 2023 Society of Chemical Industry.

Induction of Redox-Mediated Cell Death in ER-Positive and ER-Negative Breast Cancer Cells by a Copper(II)-Phenolate Complex: An In Vitro and In Silico Study.

This research was aimed at finding the cytotoxic potential of the mixed ligand copper(II) complex [Cu(tdp)(phen)](ClO4)-where H(tdp) is the tetradentate ligand 2-[(2-(2-hydroxyethylamino)-ethylimino)methyl]phenol, and phen is 1,10-phenanthroline-to two genotypically different breast cancer cells, MCF-7 (p53+ and ER+) and MDA-MB-231 (p53- and ER-). The complex has been already shown to be cytotoxic to ME180 cervical carcinoma cells. The special focus in this study was the induction of cell death by apoptosis and necrosis, and its link with ROS. The treatment brought about nuclear fragmentation, phosphatidylserine externalization, disruption of mitochondrial trans-membrane potential, DNA damage, cell cycle arrest at sub-G1 phase, and increase of ROS generation, followed by apoptotic death of cells during early hours and a late onset of necrosis in the cells surviving the apoptosis. The efficacy of the complex against genotypically different breast cancer cells is attributed to a strong association through p53-mitochondrial redox-cell cycle junction. The ADMET properties and docking of the complex at the active site of Top1 are desirable attributes of a lead molecule for development into a therapeutic. Thus, it is shown that the copper(II)-phenolate complex[Cu(tdp)(phen)]+ offers potential to be developed into a therapeutic for breast cancers in general and ER-negative ones in particular.

Synthesis of SiO2 nanostructures from Pennisetum glaucum and their effect on osteogenic differentiation for bone tissue engineering applications.

Silica nanostructures were fabricated from Pennisetum glaucum (pearl millet) seed husk by acid-pretreatment and calcination. The fabricated silica nanostructure (SN) functional groups, crystalline nature, surface morphology, and particle size were analyzed by Fourier transform infrared spectroscopy, X-ray diffraction, scanning electron microscopy, and transmission electron microscopy, respectively. Additionally, the cytocompatibility of SNs was analyzed on human mesenchymal stem cells (hMSCs) in an MTT assay, propidium iodine (PI) staining, and acridine orange/ethidium bromide (AO/EB) staining. We observed peaks at 1090 and 800 cm-1, which were assigned to symmetric, asymmetric, and bending vibrations of O-Si-O. The SNs showed an amorphous nature with a spherical shape and were 20-60 nm in diameter. The MTT assay results indicated that SNs exhibited cytocompatibility in hMSCs. The PI staining and AO/EB staining results suggested that SNs do not affect nuclear morphology at up to 400 µg/mL. Furthermore, SNs effect on osteogenic differentiation in hMSCs was studied. These results indicate that SNs induced osteogenic differentiation in hMSCs by upregulation of ALP, BSP, ON and RUNX2 genes. Our process could valorize the Pennisetum glaucum agricultural residues to high value products for bone tissue engineering applications.

Antimicrobial activity of nanoemulsion on drug-resistant bacterial pathogens.

The appearance of drug-resistant (DR) bacteria in the community is a crucial development, and is associated with increased morbidity, mortality, healthcare costs, and antibiotic use. Natural oil nanoemulsions (NEs) have potential for antimicrobial applications. In the present study, we determined the antimicrobial activity of an NE against DR bacterial pathogens in vitro. The NE comprised Cleome viscosa essential oil, Tween 80 nonionic surfactant, and water. We found that an NE with a droplet size of 7 nm and an oil:surfactant (v/v) ratio of 1:3 was effective against methicillin-resistant Staphylococcus aureus (MRSA), DR Streptococcus pyogenes, and DR extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Fourier-transform infrared (FTIR) spectroscopy revealed that NE treatment modified the functional groups of lipids, proteins, and nucleic acids in DR bacterial cells. Scanning electron microscopy (SEM) showed damage to the cell membranes and walls of NE-treated DR bacteria. These alterations were caused by bioactive compounds with wide-spectrum enzyme-inhibiting activity in the NE, such as ß-sitosterol, demecolcine, campesterol, and heneicosyl formate. The results suggest that the nanoemulsion is effective against DR bacteria, and acts by inhibiting the drug efflux mechanism of DR strains.

Multicomponent Domino Synthesis, Anticancer Activity and Molecular Modeling Simulation of Complex Dispirooxindolopyrrolidines.

A series of spirooxindolopyrrolidine fused N-styrylpiperidone heterocyclic hybrids has been synthesized in excellent yield via a domino multicomponent protocol that involves one-pot three component 1,3-dipolar cycloaddition and concomitant enamine reactions performed in an inexpensive ionic liquid, namely 1-butyl-3-methylimidazolium bromide ([bmim]Br). Compounds thus synthesized were evaluated for their cytotoxicity against U-937 tumor cells. Interestingly; compounds 5i and 5m exhibited a better cytotoxicity than the anticancer drug bleomycin. In addition; the effect of the synthesized compounds on the nuclear morphology of U937 FaDu cells revealed that treatment with compounds 5a⁻m led to their apoptotic cell death.

Aluminum oxide nanoparticles alter cell cycle progression through CCND1 and EGR1 gene expression in human mesenchymal stem cells.

Aluminum oxide nanoparticles (Al2 O3 -NPs) are important ceramic materials that have been used in a variety of commercial and industrial applications. However, the impact of acute and chronic exposure to Al2 O3 -NPs on the environment and on human health has not been well studied. In this investigation, we evaluated the cytotoxic effects of Al2 O3 -NPs on human mesenchymal stem cells (hMSCs) by using a cell viability assay and observing cellular morphological changes, analyzing cell cycle progression, and monitoring the expression of cell cycle response genes (PCNA, EGR1, E2F1, CCND1, CCNC, CCNG1, and CYCD3). The Al2 O3 -NPs reduced hMSC viability in a dose- and time-dependent manner. Nuclear condensation and fragmentation, chromosomal DNA fragmentation, and cytoplasmic vacuolization were observed in Al2 O3 -NP-exposed cells. The nuclear morphological changes indicated that Al2 O3 -NPs alter cell cycle progression and gene expression. The cell cycle distribution revealed that Al2 O3 -NPs cause cell cycle arrest in the sub-G0-G1 phase, and this is associated with a reduction in the cell population in the G2/M and G0/G1 phases. Moreover, Al2 O3 -NPs induced the upregulation of cell cycle response genes, including EGR1, E2F1, and CCND1. Our results suggested that exposure to Al2 O3 -NPs could cause acute cytotoxic effects in hMSCs through cell cycle regulatory genes.

Green synthesis of bimetallic Au@Pt nanostructures and their application for proliferation inhibition and apoptosis induction in human cervical cancer cell.

Bimetallic Au@Pt nanostructures (Au@Pts) are potential candidates for optical, electrical, catalytic and biological applications. However, methods for the fabrication of Au@Pts using total tea polyphenols (TPPs), studies of the mechanism of action of Au@Pts on biological systems and studies on the application of Au@Pts in cancer diagnosis and therapy are sparse. In this study, we developed a simple, eco-friendly and low-cost method for the synthesis of Au@Pts to examine the cytotoxic effect of these Au@Pts on human cervical cancers in vitro. The gold and platinum ions were successfully reduced simultaneously using TPPs at room temperature. The prepared Au@Pts were characterized using UV-Vis spectrophotometery, X-ray diffractometery (XRD), energy-dispersive X-ray spectroscopy (EDS), and transmission electron microscopy (TEM). EDS and XRD confirmed the formation of the Au@Pt. Formation of Au@Pts with a size of 5-20 nm was confirmed using TEM. The cytotoxic properties of the Au@Pts were evaluated in human cervical cancer cells (SiHa). The cell viability results revealed that Au@Pts induce cell death in a dose- and time-dependent manner. The morphological features of the Au@Pt-exposed SiHa cells were observed and indicated cell death via cell shrinkage, intranucleosomal DNA fragmentation and chromatin condensation. During progression of the different phases of the cell cycle, the proportion of cells in the G2/M phase of the treated SiHa cells was significantly increased, which strongly confirmed that the Au@Pts induced apoptosis through the G2/M phase check points. Our findings demonstrate the activity of Au@Pts against cervical cancer cells and reveal strategies for the development of highly active bimetallic nanostructures for cancer therapeutics.

Effects of titanium dioxide nanoparticles isolated from confectionery products on the metabolic stress pathway in human lung fibroblast cells.

Titanium dioxide (TiO2) is a common additive in many foods, pigments, personal care products, and other consumer products used in daily life. Despite the widespread use of nanoscale TiO2 and composites of nanoscale TiO2 in the food industry, there is a serious lack of awareness of the toxicity of TiO2 nanoparticles (NPs) among consumers and manufacturers. There is an urgent need for toxicological studies of TiO2 NPs. TiO2 food additives separated from marketed foods were characterized by transmission electron microscopy. In addition, the effects of TiO2 NPs on metabolic stress in WI-38 cells were analyzed. Cell viability, total ROS, mitochondrial transmembrane potential (ΔψM), cell cycle, and metabolism-related gene expression were analyzed. The results indicate that TiO2 NPs have a significant concentration-dependent toxic effect in lung cells. The ΔψM, the intracellular ROS level, and the stages of the WI-38 cell cycle were altered by increasing TiO2 concentrations after exposure for 24 and 48 h relative to the control. Cytochrome P450 1A, GSTM3, and glutathione S-transferase A4 upregulation in response to the TiO2 NPs was observed. These findings suggest that the toxicity of TiO2 from confectionery products in WI-38 cells may be mediated through an increase in oxidative stress. The results of this study clearly demonstrate the nanotoxicological effects of TiO2 on WI-38 cells and will be useful for nanotoxicological indexing.

Presence of nanosilica (E551) in commercial food products: TNF-mediated oxidative stress and altered cell cycle progression in human lung fibroblast cells.

Silica (E551) is commonly used as an anti-caking agent in food products. The morphology and the dimension of the added silica particles are not, however, usually stated on the food product label. The food industry has adapted nanotechnology using engineered nanoparticles to improve the quality of their products. However, there has been increased debate regarding the health and safety concerns related to the use of engineered nanoparticles in consumer products. In this study, we investigated the morphology and dimensions of silica (E551) particles in food. The silica content of commercial food products was determined using inductively coupled plasma optical emission spectrometry. The result indicates that 2.74-14. 45 µg/g silica was found in commercial food products; however, the daily dietary intake in increase causes adverse effects on human health. E551 was isolated from food products and the morphology, particle size, crystalline nature, and purity of the silica particles were analyzed using XRD, FTIR, TEM, EDX and DLS. The results of these analyses confirmed the presence of spherical silica nanoparticles (of amorphous nature) in food, approximately 10-50 nm in size. The effects of E551 on human lung fibroblast cell viability, intracellular ROS levels, cell cycle phase, and the expression levels of metabolic stress-responsive genes (CAT, GSTA4, TNF, CYP1A, POR, SOD1, GSTM3, GPX1, and GSR1) were studied. The results suggest that E551 induces a dose-dependent cytotoxicity and changes in ROS levels and alters the gene expression and cell cycle. Treatment with a high concentration of E551 caused significant cytotoxic effects on WI-38 cells. These findings have implications for the use of these nanoparticles in the food industry.

Biogenic silica-metal phosphate (metal = Ca, Fe or Zn) nanocomposites: fabrication from rice husk and their biomedical applications.

In this investigation, we fabricated biogenic silica-metal phosphate nanocomposites (BSMPNs) using rice husk from agricultural waste as a silica source. The morphologies and dimensions of the synthesized nanocomposites were analyzed using transmission electron microscopy (TEM). Fourier-transform infrared spectroscopy results confirmed that metal phosphate crystals were formed with the biogenic silica. The X-ray diffraction patterns of the BSMPNs showed the presence of hexagonal calcium and iron phosphate and orthorhombic zinc phosphate nanoparticles embedded in the matrix of biogenic silica. The TEM images suggested that spherical and irregularly shaped tiny particles with dimensions between 50 and 100 nm were dispersed in the biogenic silica. The in vitro biological properties of the nanocomposites were studied by a cell viability assay and through the analysis of microscopy images. The cytocompatibility studies proved that the material was nontoxic and had excellent biocompatibility with human mesenchymal stem cells. The synthetic route for these nanocomposites is interesting and may be helpful in the fabrication of various novel silica-based composites and in the exploitation of eco-friendly agricultural biomass. Our results revealed that these nanocomposites can be used in bone tissue engineering.

Understanding the Interaction between Nanomaterials Originated from High-Temperature Processed Starch/Myristic Acid and Human Monocyte Cells.

High-temperature cooking approaches trigger many metabolically undesirable molecule formations, which pose health risks. As a result, nanomaterial formation has been observed while cooking and reported recently. At high temperatures, starch and myristic acid interact and lead to the creation of nanomaterials (cMS-NMs). We used a non-polar solvent chloroform to separate the nanomaterials using a liquid-liquid extraction technique. The physico-chemical characterization was carried out using dynamic light scattering (DLS), transmission electron microscopy (TEM), thermogravimetric analysis (TGA), and Fourier-transform infrared spectroscopy (FTIR). To determine the biological impact of these nanomaterials using different in vitro assays, including a cell viability assay, microscopic staining, and gene expression analysis, we adopted the THP-1 cell line as an in vitro monocyte model in our study. The TEM images revealed that fabricated cMS nanomaterials are smaller than 100 nm in diameter. There were significant concerns found in the cytotoxicity assay and gene expression analysis. At concentrations of 100-250 µg/mL, the cMS-NMs caused up to 95% cell death. We found both necrosis and apoptosis in cMS-NMs treated THP-1 cells. In cMS-NMs-treated THP-1 cells, we found decreased expression levels in IL1B and NFKB1A genes and significant upregulation in MIF genes, suggesting a negative immune response. These findings strongly suggest that cMS-NMs originated from high-temperature food processing can cause adverse effects on biological systems. Therefore, charred materials in processed foods should be avoided in order to minimize the risk of health complications.

Co-exposure to commercial food product ingredient E341 and E551 triggers cytotoxicity in human mesenchymal stem cells.

Several nano-toxicological studies have assessed the prospective health risks of engineered nanostructures. Still, nanoscale ingredients from food products are not explored well, and only a few have attended to the possible effects of food additive-based nanoparticles in food. The physicochemical properties of food additives and their fate on human health are still unknown. To fill this knowledge gap, we examined the physicochemical characteristics of food product isolate E341/E551. Additionally, we assessed the consequence of these nanoscale E341 and E551 as co-exposure on human mesenchymal stem cells (hMSCs). The transmission electron microscope (TEM) images revealed that food product isolate (E341/E551) consists of nanoscale particles. The E551 and E341 have 20-50 nm and 70-200 nm diameters, respectively. Co-exposure of food additives SiO2 (E551) and Tricalcium phosphate (E341) effect on the cell viability, morphology, mitochondrial membrane potential, and reactive oxygen species (ROS) level of hMSCs were studied. The cell viability reduction, mitochondrial membrane potential loss, and ROS generation in E341/E551 co-exposed cells were observed. Our study suggests that E341/E551 co-exposure elevated the ROS level and mitochondrial membrane potential depletion at a high dose. The oxidative stress-related genes MDM3, TNFSF10, and POR have exhibited significant upregulation in the E341/E551 treatment group. These results conclude that long-term over-exposure to E341/E551 may be triggers health risks in a human. Further in vivo studies are required for food industry implications due to nanoscale ingredients in E341 and E551.

Association of CYP2R1 and CYP27B1 genes with the risk of obesity and vitamin D metabolism in Saudi women.

BACKGROUND: Epigenome, genetic variants, and other environmental factors involved in gene regulation are highly inter-dependent in several chronic diseases, including obesity, cardiovascular disease, and diabetes. The present study aimed at testing the associations and the mechanism involved in silencing of CYP2R1 gene in normal and obese Saudi women patients. Height, weight, BMI, 25-hydroxy vitamin D, parathyroid hormone, glycemic status, and lipid profile (TG, LDL, HDL, and TC) of CYP2R1 were measured in 100 women (31 normal and 69 obese patients). RESULTS: Our result shows that hypermethylation in site 2 of the CYP2R1 gene with body weight (p < 0.004), BMI (p < 0.002), waist circumference (p < 0.002), total-LDL (p < 0.027), total cholesterol (p < 0.022), and vitamin D (VD) (close to borderline significance p < 0.06) and site 4 of CYP2R1 with LDL (p < 0.041) in the four tested sites among normal and obese women was significantly associated. Moreover, we tested five different CpG sites in the CYP27B1 gene where site 5 correlated significantly with VD levels. CONCLUSION: Our present study clearly indicates that hypermethylation of specific sites in the CYP2R1 and CYP27B1 genes might regulate gene expression with special reference to the risk of obesity and vitamin D metabolism.

Unveiling the Biocompatible Properties of Date Palm Tree (Phoenix dactylifera L.) Biomass-Derived Lignin Nanoparticles.

Searching for sustainable, ecofriendly, and renewable precursors for nanostructured material synthesis is a fascinating area pertaining to feasibility in various applications. Especially, lignin-based material preparation is essential for unraveling the usage of lignin by valorization. Hence, we have synthesized lignin nanoparticles (LNPs) using date palm tree (Phoenix dactylifera L.) biomass as a precursor in this investigation. The LNP's morphological and thermal features were assessed. Moreover, we have evaluated the LNP's cytocompatibility properties by adopting in vitro approach. The P. dactylifera L. (PD) biomass-derived LNP's morphological features show a spherical shape with a 10-100 nm diameter. The LNPs have a decreased cell viability of ∼8% at a high concentration exposure to human mesenchymal stem cells (hMSCs) for 48 h. However, the LNPs do not cause any cellular and nuclear morphology changes in hMSCs. The mitochondrial membrane potential assessment results confirm healthy mitochondria with high mitochondrial membrane potential in LNP-treated cells. The intracellular reactive oxygen species (ROS) generation assay results revealed that LNPs do not trigger ROS generation in hMSCs. We examined the upregulation of GSTM3 and GSR genes and the downregulation of SOD1 genes in LNP-treated hMSCs, but no significant changes were observed. Our study concluded that PD biomass-derived LNPs have a good cytocompatibility and an antioxidant property. Thus, they can be applicable for various biological, cosmetic, and environmental applications.

Plumbagin triggers redox-mediated autophagy through the LC3B protein in human papillomavirus-positive cervical cancer cells.

INTRODUCTION: In this study, we analyzed the effect of plumbagin (PL) on cultured SiHa cervical cancer cells using fluorescence microscopy and flow cytometry techniques to identify the mode of cell death and to elucidate whether cells die through apoptosis or non-apoptosis. MATERIAL AND METHODS: The cell death was analyzed using MTT assay. The cellular morphological changes were assessed using acridine orange/ethidium bromide dual staining. DNA damage and cell cycle progression were analyzed using a comet assay and flow cytometry respectively. RESULTS: Morphological and cytological features revealed that PL induced autophagic cell death in cancer cells. The results of a cell cycle analysis indicated that the proportion of cells in sub-G0 phase increased. Translocation of LC-3B protein from the cytoplasm to the autophagosome was found in 31% of PL-treated cells, suggesting that PL provoked autophagic cell death. In this study, it was observed that plumbagin treatment caused cleavage of DNA in SiHa cancer cells, and morphological analysis provided very strong evidence supporting the occurrence of autophagic cell death as a result of plumbagin treatment. CONCLUSIONS: In addition, a Cytoscape-based protein-PL interaction network analysis provided very strong evidence in support of the specific mode of cell death in the context of autophagy, which has also been one of the desired endpoints in human papillomavirus-positive cervical cancer therapy and apoptotic cell death-resistant cancer treatment. Thus, this study is the first to test PL against the SiHa cervical cancer cell line, providing leads for further testing on non-apoptotic cell death for application in cervical cancer management.

Ternary dinuclear copper(II) complexes of a hydroxybenzamide ligand with diimine coligands: the 5,6-dmp ligand enhances DNA binding and cleavage and induces apoptosis.

The dinuclear copper(II) complexes [Cu(2)(LH)(2)(diimine)(2)(ClO(4))(2)](ClO(4))(2) (1-4), where LH = 2-hydroxy-N-[2-(methylamino)ethyl]benzamide and diimine = 2,2'-bipyridine (bpy; 1), 1,10-phenanthroline (phen; 2), 5,6-dimethyl-1,10-phenanthroline (5,6-dmp; 3), and dipyrido[3,2-d:2',3'-f]quinoxaline (dpq; 4), have been isolated and characterized. The X-ray crystal structure of complex 1 contains two copper(II) centers bridged by the phenolate moiety of the amide ligand. All of the complexes display a ligand-field band (630-655 nm) and the PhO(-)-to-Cu(II) ligand-to-metal charge-transfer band (405-420 nm) in solution. Absorption and emission spectral studies and viscosity measurements indicate that complex 4 interacts with calf thymus DNA more strongly than all of the other complexes through strong partial intercalation of the extended planar ring (dpq) with a DNA base stack. Interestingly, 3 exhibits a DNA binding affinity higher than 2, suggesting the involvement in hydrophobic interaction of coordinated 5,6-dmp with the DNA surface. In contrast to the increase in relative viscosities of DNA bound to 2-4, a decrease in viscosity of DNA bound to 1 is observed, indicating a shortening of the DNA chain length through formation of kinks or bends. All of the complexes exhibit an ability to cleave DNA (pUC19 DNA) in a 5% DMF/5 mM Tris-HCl/50 mM NaCl buffer at pH 7.1 in the absence of an oxidant at 100 µM complex concentration, which varies as 4 > 2 > 1 > 3. The order of DNA the cleavage ability at 30 µM concentration in the presence ascorbic acid is 4 > 2 > 1 > 3, and, interestingly, 4 alone shows an ability to convert supercoiled DNA into nicked-coiled DNA even at 6 µM concentration, beyond which complete degradation is observed and the pathway of oxidative DNA cleavage involves hydroxyl radicals. In the presence of distamycin, all of the complexes, except 3, show decreased DNA cleavage activity, suggesting that the complexes prefer to bind in the DNA minor groove. All of the complexes exhibit prominent DNA cleavage even at very low concentrations (nM) in the presence of H(2)O(2) as an activator, with the order of cleavage efficiency being 3 > 2 > 4 > 1. Studies on the anticancer activity toward HEp-2 human larynx cell lines reveal that the ability of the complexes to kill the cancer cell lines varies as 3 > 4 > 2 > 1. Also, interestingly, the IC(50) value of 3 is lower than that of cisplatin, suggesting that the hydrophobicity of methyl groups on the 5 and 6 positions of the complex enhances the anticancer activity. The mode of cell death effected by the complex has been explored by using various biochemical techniques like comet assay, mitochondrial membrane potency, and Western blotting. The complex has been found to induce nuclear condensation and fragmentation in cell lines. Also, it triggers activation of caspases by releasing cytochrome c from mitochondria to cytosol, suggesting that it induces apoptosis in cells via the mitochondrial pathway.

Simultaneous fabrication of carbon nanodots and hydroxyapatite nanoparticles from fish scale for biomedical applications.

Fish industries and markets produce large quantities of fish scales, skins, shells, and bone wastes post processing that contaminate the environment and cause health risks in humans. In this context, we have developed a novel and simple integrated process to valorize the Lethrinus lentjan fish scales by fabricate carbon nanodots (CDs) and hydroxyapatite nanoparticles (HA NPs) simultaneously. The fish scale treatment was carried out by hydrothermal method at 280 °C that produced CDs and HA NPs simultaneously. Under hydrothermal treatment, organic and inorganic substances of fish scale is transformed to CDs and HA NPs respectively. As TEM images confirmed that fish scale derived CDs were spherically shaped and ~3 to 15 nm in size. The CDs exhibited excitation-dependent emission in photoluminescence. The HA NPs were ~8 to 12 nm in diameter and ~50 to 100 nm in length with rod shape. Also, HA NPs possess spherical shape nanostructures with 15-50 nm in diameter. Furthermore, we assessed the cytotoxic behavior of synthesized nanostructures using the MTT assay and acridine orange/ethidium bromide (AO/EB) staining. These results showed that synthesized CDs and HA NPs did not cause significant changes in cell viability and morphology, indicating biocompatibility. Additionally, the synthesized CDs and HA NPs were exploited as fluorescent probes for cellular imaging and osteogenic differentiation of stem cells respectively. Overall, the study results indicate that low-cost fish waste was valorized by producing CDs and HA NPs concurrently. The synthesized nanostructures can be applicable for bio-imaging and bone tissue engineering applications.

Induction of cell death by ternary copper(II) complexes of L-tyrosine and diimines: role of coligands on DNA binding and cleavage and anticancer activity.

The mononuclear mixed ligand copper(II) complexes of the type [Cu(L-tyr)(diimine)](ClO(4)), where tyr is L-tyrosine and diimine is 2,2'-bipyridine (bpy) (1), 1,10-phenanthroline (phen) (2), 5,6-dimethyl-1,10-phenanthroline (5,6-dmp) (3), and dipyrido[3,2-d:2',3'-f]quinoxaline (dpq) (4), have been isolated and characterized by analytical and spectral methods. In the X-ray crystal structure 3 Cu(II) possesses a distorted square pyramidal coordination geometry with the two nitrogen atoms of 5,6-dmp ligand and the amine nitrogen and carboxylate oxygen atoms of L-tyrosine located at the equatorial sites and the coordinated water molecule present in the apical position. The electronic absorption and electron paramagnetic resonance (EPR) spectral parameters reveal that the complexes retain their square-based geometries even in solution. All of the complexes display a ligand field band in the visible region (600-700 nm) in Tris-HCl/NaCl buffer (5:50 mM) at pH 7.2 and also axial EPR spectra in acetonitrile at 77 K with g(parallel) > g(perpendicular) indicating a d(x(2)-y(2)) ground state. The g(parallel) and A(parallel) values of 2.230 and (170-180) x 10(-4) cm(-1), respectively, conform to a square-based CuN(3)O coordination chromophore, which is consistent with the X-ray crystal structure of 3. The interaction of the complexes with calf thymus DNA (CT DNA) has been explored by using physical methods to propose modes of DNA binding of the complexes. Absorption (K(b)) and emission spectral studies and viscosity measurements indicate that 4 interacts with DNA more strongly than all of the other complexes through partial intercalation of the extended planar ring of dpq with DNA base stack. Interestingly, complex 3 exhibits a DNA binding affinity that is higher than that of 2, which suggests the involvement of 5,6-dimethyl groups on the phen ring in hydrophobic interaction with DNA surface. In contrast with the increase in relative viscosities of DNA bound to 2-4, the viscosity of DNA bound to 1 decreases, indicating the shortening of the DNA chain length by means of the formation of kinks or bends. All complexes exhibit effective DNA (pUC19 DNA) cleavage at 100 microM complex concentrations, and the order of DNA cleavage ability varies as 3 > 2 > 4 > 1. Interestingly, 3 exhibits a DNA cleavage rate constant that is higher than that of the other complexes only at 100 microM concentration, whereas 4 exhibits the highest cleavage rate constant at 80 microM complex concentration. The oxidative DNA cleavage follows the order 4 > 3 > 2 > 1. Mechanistic studies reveal that the DNA cleavage pathway involves hydroxyl radicals. Interestingly, only 4 displays efficient photonuclease activity upon irradiation with 365 nm light, which occurs through double-strand DNA breaks involving hydroxyl radicals. Furthermore, cytotoxicity studies on the nonsmall lung cancer (H-460) cell line show that the IC(50) values of 2-4 are more or less equal to cisplatin for the same cell line, indicating that they have the potential to act as very effective anticancer drugs in a time-dependent manner. The study of cytological changes reveals the higher induction of apoptosis and mitotic catastrophe for 4 and 3, respectively. The alkaline single-cell gel electrophoresis (comet assay), DNA laddering, and AO/EB and Hoechst 33258 staining assays have also been employed in finding the extent of DNA damage. Flow cytometry analysis shows an increase in the percentage of cells with apoptotic morphological features in the sub-G(0)/G(1) phase for 4, whereas it shows mitotic catastrophe for 3.