A549 Human Lung Carcinoma Research Articles

Resveratrol inhibits MUC5AC expression by regulating SPDEF in lung cancer cells

BackgroundMUC5AC was recently identified to play important roles in the proliferation and metastasis of malignant mucinous lung tumor cells. Resveratrol (Res), a natural compound with anticancer effects in lung cancer cells, has been reported to inhibit mucin production in airway epithelial cells. This study aimed to investigate the inhibitory effect of Res on MUC5AC expression in lung mucinous adenocarcinoma cells and the potential mechanisms. MethodsMucus-producing A549 human lung carcinoma cells were used to test the effects of Res on SPDEF and MUC5AC expression. Gene and protein expression was assessed by real-time quantitative PCR (qPCR), immunofluorescence and western blotting assays. SPDEF lentivirus was used to upregulate SPDEF expression levels in mucus-producing A549 human lung carcinoma cells. Cell proliferation was assessed by Cell Counting Kit-8 (CCK-8) assay. ResultsRes decreased MUC5AC expression in an SPDEF-dependent manner in mucus-producing A549 human lung carcinoma cells, and this change was accompanied by decreased ERK expression and AKT pathway activation. Moreover, SPDEF was found to be overexpressed in lung adenocarcinoma (LUAD), especially in mucinous adenocarcinoma. In-vitro functional assays showed that overexpression of SPDEF reduced the chemosensitivity of A549 cells to cisplatin (DDP). In addition, Res treatment increased A549 cell chemosensitivity to DDP by inhibiting the SPDEF-MUC5AC axis. ConclusionOur results indicate that the SPDEF-MUC5AC axis is associated with DDP sensitivity, and that Res decreases SPDEF and MUC5AC expression by inhibiting ERK and AKT signaling in A549 cells, which provides a potential pharmacotherapy for the prevention and therapeutic management of mucinous adenocarcinoma.

Optimization of PhysicoChemical Parameters for Production of Cytotoxic Secondary Metabolites and Apoptosis Induction Activities in the Culture Extract of a Marine Algal-Derived Endophytic Fungus Aspergillus sp.

The endophytic fungal community in the marine ecosystem has been demonstrated to be relevant source of novel and pharmacologically active secondary metabolites. The current study focused on the evaluation of cytotoxic and apoptosis induction potential in the culture extracts of endophytic fungi associated with Sargassum muticum, a marine brown alga. The cytotoxicity of the four marine endophytes, Aspergillus sp., Nigrospora sphaerica, Talaromyces purpureogenus, and Talaromyces stipitatus, was evaluated by the MTT assay on HeLa cells. Further, several physicochemical parameters, including growth curve, culture media, and organic solvents, were optimized for enhanced cytotoxic activity of the selected extract. The Aspergillus sp. ethyl acetate extract (ASE) showed maximum cytotoxicity on multiple cancer cell lines. Chemical investigation of the metabolites by gas chromatography–mass spectroscopy (GC-MS) showed the presence of several compounds, including quinoline, indole, 2,4-bis(1,1-dimethylethyl) phenol, and hexadecenoic acid, known to be cytotoxic in ASE. The ASE was then tested for cytotoxicity in vitro on a panel of six human cancer cell lines, namely, HeLa (cervical adenocarcinoma), MCF-7 (breast adenocarcinoma), Hep G2 (hepatocellular carcinoma), A-549 (lung carcinoma), A-431 (skin/epidermis carcinoma), and LN-229 (glioblastoma). HeLa cells were most vulnerable to ASE treatment with an IC50 value of 24 ± 2 μg/ml. The mechanism of cytotoxicity exhibited by the ASE was further investigated on Hela cells. The results showed that the ASE was capable of inducing apoptosis in HeLa cells through production of reactive oxygen species, depolarization of mitochondrial membrane, and activation of the caspase-3 pathway, which shows a possible activation of the intrinsic apoptosis pathway. It also arrested the HeLa cells at the G2/M phase of the cell cycle, eventually leading to apoptosis. Through this study, we add to the knowledge about the marine algae associated with fungal endophytes and report its potential for purifying specific compounds responsible for cytotoxicity.

Saturated Oxo Fatty Acids (SOFAs): A Previously Unrecognized Class of Endogenous Bioactive Lipids Exhibiting a Cell Growth Inhibitory Activity

The discovery of novel bioactive lipids that promote human health is of great importance. Combining "suspect" and targeted lipidomic liquid chromatography-high-resolution mass spectrometry (LC-HRMS) approaches, a previously unrecognized class of oxidized fatty acids, the saturated oxo fatty acids (SOFAs), which carry the oxo functionality at various positions of the long chain, was identified in human plasma. A library of SOFAs was constructed, applying a simple green photochemical hydroacylation reaction as the key synthetic step. The synthesized SOFAs were studied for their ability to inhibit in vitro the cell growth of three human cancer cell lines. Four oxostearic acids (OSAs) were identified to inhibit the cell growth of human lung carcinoma A549 cells. 6OSA and 7OSA exhibited the highest cell growth inhibitory potency, suppressing the expression of both STAT3 and c-myc, which are critical regulators of cell growth and proliferation. Thus, naturally occurring SOFAs may play a role in the protection of human health.

In Vitro Antibacterial, Anti-Adhesive and Anti-Biofilm Activities of Krameria lappacea (Dombey) Burdet & B.B. Simpson Root Extract against Methicillin-Resistant Staphylococcus aureus Strains.

Methicillin-resistant Staphylococcus aureus (MRSA) represents a serious threat to public health, due to its large variety of pathogenetic mechanisms. Accordingly, the present study aimed to investigate the anti-MRSA activities of Krameria lappacea, a medicinal plant native to South America. Through Ultra-High-Performance Liquid Chromatography coupled with High-Resolution Mass spectrometry, we analyzed the chemical composition of Krameria lappacea root extract (KLRE). The antibacterial activity of KLRE was determined by the broth microdilution method, also including the minimum biofilm inhibitory concentration and minimum biofilm eradication concentration. Besides, we evaluated the effect on adhesion and invasion of human lung carcinoma A549 cell line by MRSA strains. The obtained results revealed an interesting antimicrobial action of this extract, which efficiently inhibit the growth, biofilm formation, adhesion and invasion of MRSA strains. Furthermore, the chemical analysis revealed the presence in the extract of several flavonoid compounds and type-A and type-B proanthocyanidins, which are known for their anti-adhesive effects. Taken together, our findings showed an interesting antimicrobial activity of KLRE, giving an important contribution to the current knowledge on the biological activities of this plant.

Synthesis, Characterization, DNA Binding, Cleavage, Antibacterial, In vitro Anticancer and Molecular Docking Studies of Ni(II), Cu(II) and Zn(II) Complexes of 3,4,5-Trimethoxy-N-(3-Hydroxy-5-(Hydroxymethyl)-2-Methylpyridin-4-yl)methylene)Benzohydrazide

The Schiff base ligand (L), 3,4,5-Trimethoxy-N-((3-hydroxy-5-(hydroxymethyl)-2-methylpyridin-4-yl)methylene)benzohydrazide (PLTMBH) was prepared by condensation of pyridoxal and 3,4,5-Trimethoxybenzohydrazide. The metal complexes of the ligand with Ni(II), Cu(II) and Zn(II) ions (M) were synthesized. The complexes were characterized by various spectroscopic IR, 1H-NMR, UV, LC–MS and ESR studies and analytical methods as elemental analysis, thermal analysis, molar conductance and magnetic susceptibility measurements. Based on the results, the complexes were assigned distorted octahedral geometry with a metal-to-ligand ratio, 1:2 (ML2). The interaction of the metal complexes with calf thymus (CT) DNA was investigated by electronic absorption and fluorescence emission spectra, viscosity measurements and molecular docking studies. The electronic and fluorescence spectra indicated that the metal complexes can bind to DNA with binding constant (Kb) of 0.819 × 104, 1.014 × 104and 0.427 × 104 M−1 for Ni(II), Cu(II) and Zn(II) complexes, respectively. The viscosity studies suggested groove mode of binding of the complexes with CT DNA. The docking studies of metal complexes with DNA were performed to assess possible mode of interaction, which also supported groove mode of binding for all the complexes. The complexes also showed significant cleavage ability of plasmid pBR322 DNA. The metal complexes showed good antibacterial activity, while the ligand showed moderate activity. The in vitro anticancer assay for the Ni(II) and Cu(II) complexes was performed by standard MTT assay method, against HeLa-Human cervical carcinoma cells, MCF-7-Human breast carcinoma cells and A549-Human lung carcinoma cells. The study indicated appreciable anticancer activity of the complexes.

Synthesis of New Biscoumarin Derivatives, In Vitro Cholinesterase Inhibition, Molecular Modelling and Antiproliferative Effect in A549 Human Lung Carcinoma Cells.

A series of novel C4-C7-tethered biscoumarin derivatives (12a–e) linked through piperazine moiety was designed, synthesized, and evaluated biological/therapeutic potential. Biscoumarin 12d was found to be the most effective inhibitor of both acetylcholinesterase (AChE, IC50 = 6.30 µM) and butyrylcholinesterase (BChE, IC50 = 49 µM). Detailed molecular modelling studies compared the accommodation of ensaculin (well-established coumarin derivative tested in phase I of clinical trials) and 12d in the human recombinant AChE (hAChE) active site. The ability of novel compounds to cross the blood–brain barrier (BBB) was predicted with a positive outcome for compound 12e. The antiproliferative effects of newly synthesized biscoumarin derivatives were tested in vitro on human lung carcinoma cell line (A549) and normal colon fibroblast cell line (CCD-18Co). The effect of derivatives on cell proliferation was evaluated by MTT assay, quantification of cell numbers and viability, colony-forming assay, analysis of cell cycle distribution and mitotic activity. Intracellular localization of used derivatives in A549 cells was confirmed by confocal microscopy. Derivatives 12d and 12e showed significant antiproliferative activity in A549 cancer cells without a significant effect on normal CCD-18Co cells. The inhibition of hAChE/human recombinant BChE (hBChE), the antiproliferative activity on cancer cells, and the ability to cross the BBB suggest the high potential of biscoumarin derivatives. Beside the treatment of cancer, 12e might be applicable against disorders such as schizophrenia, and 12d could serve future development as therapeutic agents in the prevention and/or treatment of Alzheimer’s disease.

A549 cells contain enlarged mitochondria with independently functional clustered mtDNA nucleoids.

Mitochondria are commonly viewed as highly elongated organelles with regularly spaced mtDNA genomes organized as compact nucleoids that generate the local transcripts essential for production of mitochondrial ribosomes and key components of the respiratory chain. In contrast, A549 human lung carcinoma cells frequently contain apparently swollen mitochondria harboring multiple discrete mtDNA nucleoids and RNA processing granules in a contiguous matrix compartment. While this seemingly aberrant mitochondrial morphology is akin to “mito-bulbs” previously described in cells exposed to a variety of genomic stressors, it occurs in A549 cells under typical culture conditions. We provide a detailed confocal and super-resolution microscopic investigation of the incidence of such mito-bulbs in A549 cells. Most mito-bulbs appear stable, engage in active replication and transcription, and maintain respiration but feature an elevated oxidative environment. High concentrations of glucose and/or L-glutamine in growth media promote a greater incidence of mito-bulbs. Furthermore, we demonstrate that treatment of A549 cells with TGFβ suppresses the formation of mito-bulbs while treatment with a specific TGFβ pathway inhibitor substantially increases incidence. This striking heterogeneity of mitochondrial form and function may play an important role in a variety of diseases involving mitochondrial dysfunction.

RETRACTED ARTICLE: Catalytic Au/PEDOT/Pt micromotors for cancer biomarker detection and potential breast cancer treatment

The synthesis and biomedical applications of nano/micromotors have attracted great attention. In this work, preparation and characterization of catalytic gold/poly(3,4-ethylenedioxythiophene)/platinum (Au/PEDOT/Pt) micromotors were reported to present their contribution for cancer biomarker miRNA-21 detection. Potential use of these motors for possible cancer treatment was also illustrated after their biocompability had shown. At first, anti-miRNA probe immobilized Au/PEDOT/Pt micromotors (probe DNA/Au/PEDOT/Pt/MMs) were used for the sensitive and selective recognition of synthetic miRNA-21 target sequence to present the proof-of-concept. Then intracellular studies were carried out using four types of cancer cells (human breast cancer cell line, MCF-7, human colorectal adenocarcinoma cell line, HT-29, human lung carcinoma cell line, A-549 and human osteosarcoma cell line, SJSA-1). These studies illustrated the high selectivity of probe DNA/Au/PEDOT/Pt micromotors for MCF-7 and SJSA-1 cells. Later, antiproliferative and cytotoxic effects of the micromotors and their potential use for breast cancer treatment were investigated.

Development of method for creating tumor xenograft model with porous metal scaffold

Aim of the study – the development of a method for obtaining a tumor xenograft model by a subcutaneous transplantation of a porous metal scaffold populated with cultured human lung carcinoma cells. Material and methods. The study included 14 athymic male Balb c/nude mice aged 8-90 weeks, weighing 20-24 g. All animals received injections with cultured human A549 lung carcinoma cells subcutaneously into the right anterolateral area of the back. In animals of the main group (gr.1, n=4), scaffolds with a pore diameter of 0.5 mm made of titanium-aluminum-vanadium alloy using an industrial 3D printer served as carriers of tumor cells. Scaffolds were seeded with 3 million A549 culture cells, and were implanted into the recipient animals after the 7-day incubation. Results were compared with the results of the tumor culture transplantation with Matrigel (100 mcL) in two groups of animals with varying cell suspension dosages: the maximum vaccination dose for in vivo (10×106 cells per mouse, gr.2, n=5) and half the maximum dose (5×106 respectively, gr.3, n=5). Then, the dynamics of tumor growth in the groups of experimental mice was monitored for 55 days: xenograft volumes were calculated using the Shrek’s formula for an ellipsoid. At the end of the experiment, the animals were euthanized by cervical dislocation. Results. Monitoring of the dynamics of xenograft volumes demonstrated the maximal values in mice with implanted scaffolds. The slowest xenograft growth was registered in animals with the maximum vaccination dose of tumor cells with Matrigel. Histological study showed that tumor material obtained from all animals corresponded to A549 lung carcinoma. Conclusions. Porous metal scaffolds, previously incubated with A549 culture cells and implanted subcutaneously in athymic Balb c/nude mice, allows obtaining rapidly growing xenografts with histologically confirmed correspondence to the original tumor.

Tacrine-Coumarin Derivatives as Topoisomerase Inhibitors with Antitumor Effects on A549 Human Lung Carcinoma Cancer Cell Lines.

A549 human lung carcinoma cell lines were treated with a series of new drugs with both tacrine and coumarin pharmacophores (derivatives 1a–2c) in order to test the compounds’ ability to inhibit both cancer cell growth and topoisomerase I and II activity. The ability of human topoisomerase I (hTOPI) and II to relax supercoiled plasmid DNA in the presence of various concentrations of the tacrine-coumarin hybrid molecules was studied with agarose gel electrophoresis. The biological activities of the derivatives were studied using MTT assays, clonogenic assays, cell cycle analysis and quantification of cell number and viability. The content and localization of the derivatives in the cells were analysed using flow cytometry and confocal microscopy. All of the studied compounds were found to have inhibited topoisomerase I activity completely. The effect of the tacrine-coumarin hybrid compounds on cancer cells is likely to be dependent on the length of the chain between the tacrine and coumarin moieties (1c, 1d = tacrine-(CH2)8–9-coumarin). The most active of the tested compounds, derivatives 1c and 1d, both display longer chains.

Automated Capillary-Based Vacuum Pulse-Assisted Instrument for Single-Cell Acquisition and Concurrent Detachment/Adhesion Assay, A-picK.

A large body of evidence points to the importance of cell adhesion molecules in cancer metastasis. Alterations in adhesion and attachment properties of neoplastic cells are important biomarkers of the metastatic potential of cancer. Loss of intracellular adhesion is correlated with more invasive phenotype by increasing the chances of malignant cells escaping from their site of origin, promoting metastasis. Therefore, there is great demand for rapid and accurate measurements of individual cell adhesion and attachment. Current technologies that measure adhesion properties in either suspension or bulk (microfluidics) remain very complex (e.g., atomic force microscopy [AFM], optical tweezers). Moreover, existing tools cannot provide measurements for fully attached individual adherent cells as they operate outside of such a force range. Even more importantly, none of the existing approaches permit concurrent and automated single-cell adhesion measurement and collection, which prohibits direct correlation between single-cell adhesion properties and molecular profile. Here, we report a fully automated and versatile platform, A-picK, that offers single-cell adhesion assay and isolation in parallel. We demonstrate the use of this approach for a time course analysis of human lung carcinoma A549 cells and substrate-specific adhesion potential using seven different substrates, including fibronectin, laminin, poly-l-lysine, carboxyl, amine, collagen, and gelatin.

Beyond a Critical Strain Rate, Lamin-A Dilutes and Nuclei Rupture at Sites of High Curvature

Constricted cell migration, which commonly occurs in vivo during tumor metastasis, can rupture nuclei. Associated rupture often correlates with high curvature imposed by pores, probes, or small micronuclei and with nuclear entry of chromatin-binding cGAS (cyclic-GMP-AMP synthase) from the cytoplasm. Suppression of lamin-A, a main component of the nuclear lamina, has been seen to increase rupture during constricted migration, but the dynamics of lamin-A under high curvature, and the mechanism by which lamin-A protects against rupture, remain incompletely understood. Thus, we studied the effect of curvature on lamin-A organization and nuclear rupture by passively pulling detached cells into micropipettes under controlled pressure. Additionally, using live imaging in highly elongated A549 human lung carcinoma cells, we quantified lamina dilution at pole regions of cell nuclei which underwent natural shape fluctuations. Extension of a nucleus into a micropipette caused dilution of lamin-B at the leading tip of the nucleus, proportional to aspirated length L, whereas dilution of lamin-A occurred only for L > Lcritical at the same early timepoint in aspiration. in similar experiments done with siLMNA U2OS human osteosarcoma cells transfected to express low or high levels of lamin-A-GFP (∼10-fold range), both low and high lamin-A levels required a critical strain to flow. Low levels of lamin-A showed greater lamin-A dilution and more nuclear rupture versus high levels as determined by cGAS entry and chromatin herniation. in highly elongated A549 cells, lamin-A at the high-curvature pole regions was found to be enriched relative to lamin-B, consistent with the idea that stiff elastic lamin-B responds immediately to applied stress while viscous lamin-A responds above some threshold. Lamin-A requires a critical strain rate to flow, and, importantly, nuclear rupture occurs at or above this critical dilution in lamin-A.

Targeting NF-κB mediated cell signaling pathway and inflammatory mediators by 1,2-diazole in A549 cells in vitro

Lung cancer is the leading cause of cancer deaths globally. The objective of this study was to investigate the effect of 1,2-diazole (pyrazole) as an anti-cancer drug on human non-small cell lung carcinoma A549 cells. We attempt to examine the expression level of pro-inflammatory proteins such as TNF-α, NF-κB-p65, MMP-2 and E-Cadherin which are commonly associated with an inflammatory response in epithelial cells and apoptosis in A549 cells. The LPS-induced cytokines and inflammatory mediators include TNF-α, IL-6, iNOS and COX-2 levels in A549 cells and the effect of pyrazole was studied. The present study reveals that, pyrazole inhibits A549 cells by suppressing TNF-α induced MMP-2 expression, thereby inhibiting the nuclear translocation of NF-κB-p65. Pyrazole significantly up-regulate the E-cadherin level and down-regulated MMP-2 expression that could probably preventing A549 cancer cells to invade. The study further substantiated the anti-cancer property of pyrazole by regulating the above mentioned level of LPS-induced cytokines and inflammatory mediators. The observations of the present study open a possibility for the development of an effective therapeutic agent that targets inflammatory and signaling pathway mediators to challenge human non-small cell lung carcinoma.

Comparative Cytotoxicity of Selected Mikania species using Brine Shrimp Lethality Bioassay and Sulforhodamine B (SRB) Assay

This study aims to assess the comparative cytotoxic activity of the ethanolic extract of Mikania cordata (MC), Mikania micrantha (MM) and Mikania scandens (MS) (Family: Asteraceae) using brine shrimp lethality bioassay and colorimetric sulforhodamine B assay method. In SRB assay, A549 human lung carcinoma, SK-Mel-2 skin melanoma and B16F1 mouse melanoma cell lines were used. In brine shrimp assay, the LC50 for MC, MM, MS and vincristine were found to be 29.04, 15.84, 32.35, and 1.2 μg/ml, respectively. The results indicate that all the Mikania species showed moderate lethality against nauplii. In SRB assay, 50% cell growth inhibition concentration (IC50) of MC, MM, MS and cisplatin against B16-F1 were 33, 15, 39 and 6.8 μg/ml, respectively. Similar data were observed for other cell lines indicating moderate cytotoxicity of the extracts. Among the species, M. micrantha showed relatively potent cytotoxic effect followed by M. cordata and M. scandens. Similar data were observed for brine shrimp lethality bioassay and the results suggest that M. micrantha possesses highest cytotoxic potentials among all the species. Bangladesh Pharmaceutical Journal 24(1): 11-16, 2021

Studies of anticancer activity in vivo and in vitro behaviors of liposomes encapsulated iridium(III) complex.

Iridium(III) complexes have gained great attention in cancer treatment in recent years. In this paper, we designed and synthesized a new iridium(III) complex [Ir(piq)2(DQTT)](PF6) Ir1 (piq = 1-phenylisoquinoline, DQTT = 12-(1,4-dihydroquinoxalin-6-yl)-4,5,9,14-tetraazabenzo[b]triphenylene). The Ir1-loaded PEGylated liposomes (Lipo-Ir1) were prepared using the ethanol injection method. The anticancer activity of the complex and Lipo-Ir1 against SGC-7901 (human gastric adenocarcinoma), A549 (human lung carcinoma), HeLa (human cervical carcinoma), HepG2 (human hepatocellular carcinoma), BEL-7402 (human hepatocellular carcinoma), and normal NIH3T3 (mouse embryonic fibroblasts) was tested by the MTT method. The complex Ir1 shows moderate or low cytotoxicity against the selected cancer cells, whereas the Lipo-Ir1 exhibits high anticancer activity toward the same cancer cells. The apoptosis induced by Lipo-Ir1 was assayed by flow cytometry and Lipo-Ir1 induced apoptosis through increasing intracellular reactive-oxygen species levels, decreasing mitochondrial membrane potential, further promoting cytochrome c release and causing the increase of level of intracellular Ca2+. Western blot was used to detect the changes in Bcl-2 family protein and PI3K/AKT pathway proteins. The cloning experiments demonstrated that the Lipo-Ir1 can effectively inhibit cell proliferation. In vivo experiments, Lipo-Ir1 inhibited tumor growth in xenograft nude mice, and the percentage of tumor growth inhibition in vivo was 75.70%. Overall, the liposomes Lipo-Ir1 exhibits higher anticancer activity than Ir1 under the same conditions. These results indicated that Lipo-Ir1 may be a valuable resource for cancer therapy.

Al-doped zinc ferrite nanoparticles: Preparation and evaluation of thermal, structural, morphological and anticancer properties

The aim of this study was to evaluate the thermal, structural, optical, morphological and anticancer properties of ZnFe2O4 (ZFO) and AlxZn1−xFe2O4 (x = 0.05) (ZAFO) nanoparticles. Zinc ferrite nanoparticles were prepared by chemical co-precipitation method, using polyethylene glycol (PEG) as the capping agent. The synthesized pure and Al-doped ZnFe2O4 nanoparticles were annealed at different temperatures such as 500, 600, 700 and 800 °C. X-ray diffraction analysis was used to determine lattice parameters like X-ray density, oxygen position parameter, distribution of cation among tetrahedral and octahedral sites, ionic radii, and edge lengths of the tetrahedral (A) and octahedral (B) sites and micro strain values. The calculated micro strain values were found to be decreasing with increasing annealing temperatures in both ZnFe2O4 and AlxZn1−xFe2O4 (x = 0.05) samples. The FTIR results confirmed ferrites tetrahedral (~540 cm−1) and octahedral sites (~431 cm−1) metal oxygen vibrations. The morphology of the synthesized ZnFe2O4 and AlxZn1−xFe2O4 (x = 0.05) nanoparticles were studied by field emission scanning electron microscopy (FE-SEM) and particle size was found to be<100 nm. Band gap energy at different temperatures were calculated using Tauc plots and found to be decreasing with increase in annealing temperatures for both ZnFe2O4 and AlxZn1−xFe2O4 (x = 0.05) nanoparticles. The anti-cancer properties were observed at the in vitro level by MTT (3-[4, 5-dimethylthiazol-2-yl]-2, 5 diphenyltetrozolium bromide) assay against human Breast cancer cell line, MCF-7 (Human Breast adenocarcinoma) and lung cancer cell line A549 (Human Lung Carcinoma). Among the pure and Al doped samples used in the present study, the ZnFe2O4 (ZFO-3) sample annealed at 700 °C showed less viability in A 549 (Human Lung Carcinoma), whereas AlxZn1−xFe2O4 (ZAFO-1) sample annealed at 500°C showed less viability in MCF-7 (Human Breast Adenocarcinoma). Toxicity studies have shown that ZnFe2O4 and AlxZn1−xFe2O4 (x = 0.05) NPs reduced cell viability and induced cell membrane damage dose dependently in the concentration range of 25–100 µg/mL

Synthesis, crystal structures, DNA interactions, and antitumor activity of two new dinuclear copper(ii) complexes with thiazole ligand.

Two new dinuclear copper(ii) complexes, [Cu(ambt)2(cnba)4] (1) and [Cu(ambt)2(clba)4] (2) were synthesized with 2-amino-6-methoxybenzothiazole (ambt) as the main ligand. The structures of the two complexes were characterized by single-crystal XRD. The binding between CT-DNA (calf thymus DNA) and the complexes was evaluated by viscometry, electronic absorption, and fluorescence spectroscopy, and the binding constants were calculated using the Stern–Volmer equation. The complexes were intercalatively bound to CT-DNA, and [Cu(ambt)2(clba)4] having a greater binding constant than [Cu(ambt)2(cnba)4]. The two complexes had better antitumor properties against HepG2 (human hepatocellular carcinoma), A549 (human lung carcinoma), and HeLa (human cervical carcinoma) tumor cell lines than their respective ligands and cisplatin. Furthermore, [Cu(ambt)2(clba)4] had a stronger inhibitory ability on the three types of tumor cells than [Cu(ambt)2(cnba)4], which is congruent with the binding power of the complexes with DNA. Flow cytometry revealed that [Cu(ambt)2(cnba)4] and [Cu(ambt)2(clba)4] could trigger apoptosis or necrosis, arrest the HepG2 cell cycles, and cause G0/G1-phase cells to accumulate.

Luminescent cyclometalated platinum(ii) complexes with acyclic diaminocarbene ligands: structural, photophysical and biological properties.

Four new cyclometalated Pt(ii) complexes bearing acyclic diaminocarbene (ADC) ligands, [Pt(C^N)Cl{C(NHXyl)(NHR)}] [C^N = 2,6-difluorophenylpyridine (dfppy), phenylquinoline (pq); R = Pr 3a, 4a, CH2Ph 3b, 4b], were prepared by the nucleophilic attack on the isocyanide [Pt(C^N)Cl(CNXyl)] (C^N = dfppy 1, pq 2) by the corresponding amine RNH2 (R = Pr, CH2Ph). Complexes 3 show in their 1H NMR spectra in CDCl3 a notable concentration dependence, with a clear variation of the δH (NHXyl) signal, suggesting an assembling process implying donor-acceptor NHXylCl bonding, also supported by 1D-PGSE (Pulse Field Gradient Spin Echo) and 2D-DOSY (Diffusion Ordered Spectroscopy) NMR experiments in solution and X-ray diffraction studies. The intermolecular interactions in compounds 3a and 3b were studied by using Hirshfeld surface analysis and Non-Covalent Interaction (NCI) methods on their X-ray structures. Their photophysical properties were investigated by absorption and emission spectroscopies and also by TD-DFT calculations performed on 3a and 4b. These complexes show green (3) or orange (4) phosphorescence, attributed to a mixed 3IL/3MLCT excited state. The carbene ligand does not affect the emission maxima but it produces an increase of the quantum yields in relation to the isocyanide in the precursors. In fluid solutions, the emission is not concentration-dependent, but the complexes may show aggregation induced emission as detailed for complexes 3a and 4a. In addition, cytotoxicity studies in the human cell lines A549 (lung carcinoma) and HeLa (cervix carcinoma) showed good activity for these complexes and 3a, 3b and 4a exhibit a strong effect on DNA electrophoretic mobility. To the best of our knowledge, compounds 3 and 4 represent the first examples of cycloplatinated complexes bearing acyclic diamino carbenes with antiproliferative properties.

The cytotoxic effect of Synadenium grantii extract against human lung carcinoma A549 cells and its role in improvement of histopathological and biomarkers changes in Benzo(a)pyrene-induced lung cancer in rats

Lung cancer is one of the most lethal cancers which is causing up to 3 million deaths annually worldwide. Therefore, management of lung cancer needs searching for new chemopreventive agents. This work was designed to inspect the chemopreventive potential of different extracts prepared from branches and leaves of Synadenium grantii for screening their effects on lung cancer cells (A549), then the most active extract was used for combating lung cancer induced in animal model. The in vitro results showed that, the methanolic extract was the most active extract against A549 cells with a notable cytotoxicity activity (IC50: 4.30±0.44 µg/ml), which was close to the activity of standard drug, doxorubicin (IC50: 3.50±0.40 µg/ml). The results of the in vivo experiment, revealed that in B(a)P-treated group, aspartate (AST) and alanine (ALT) transaminase activities as well as the levels of urea, creatinine, alpha-fetoprotein (AFP) and Phosphotylinosital 3 Kinase (PI3K) were significantly increased comparing to control group. However, treatment with S. grantii ameliorated the increase in these parameters in both after- and before-treatment groups comparing with B(a)P-treated group. This improvement in biochemical results were also supported by improving in morphological and histopathological injuries induced by B(a)P, which indicated that methanolic extract of S. grantii has a chemoprevention effect on lung cancer.

Inhibitory Monoclonal Antibodies and Their Recombinant Derivatives Targeting Surface-Exposed Carbonic Anhydrase XII on Cancer Cells

Monoclonal and recombinant antibodies are widely used for the diagnostics and therapy of cancer. They are generated to interact with cell surface proteins which are usually involved in the development and progression of cancer. Carbonic anhydrase XII (CA XII) contributes to the survival of tumors under hypoxic conditions thus is considered a candidate target for antibody-based therapy. In this study, we have generated a novel collection of monoclonal antibodies (MAbs) against the recombinant extracellular domain of CA XII produced in HEK-293 cells. Eighteen out of 24 MAbs were reactive with cellular CA XII on the surface of live kidney and lung cancer cells as determined by flow cytometry. One MAb 14D6 also inhibited the enzymatic activity of recombinant CA XII as measured by the stopped-flow assay. MAb 14D6 showed the migrastatic effect on human lung carcinoma A549 and renal carcinoma A498 cell lines in a ‘wound healing’ assay. It did not reduce the growth of multicellular lung and renal cancer spheroids but reduced the cell viability by the ATP Bioluminescence assay. Epitope mapping revealed the surface-exposed amino acid sequence (35-FGPDGENS-42) close to the catalytic center of CA XII recognized by the MAb 14D6. The variable regions of the heavy and light chains of MAb 14D6 were sequenced and their complementarity-determining regions were defined. The obtained variable sequences were used to generate recombinant antibodies in two formats: single-chain fragment variable (scFv) expressed in E. coli and scFv fused to human IgG1 Fc fragment (scFv-Fc) expressed in Chinese Hamster Ovary (CHO) cells. Both recombinant antibodies maintained the same specificity for CA XII as the parental MAb 14D6. The novel antibodies may represent promising tools for CA XII-related cancer research and immunotherapy.