Human Lung Carcinoma Cell Line Research Articles

Enhanced Photodynamic Therapy Efficacy through Solid Lipid Nanoparticle of Purpurin-18-N-Propylimide Methyl Ester for Cancer Treatment.

Photodynamic therapy (PDT) is an innovative cancer treatment that utilizes light. When light irradiates, purpurin-18-N-propylimide methyl ester (P18 N PI ME) generates reactive oxygen species that destroy cancer cells. The hydrophobic nature of P18 N PI ME presents challenges regarding its aggregation in the body, which can affect its effectiveness. This study aimed to enhance the bioavailability and effectiveness of cancer treatment by synthesizing P18 N PI ME and formulating P18 N PI ME-loaded solid lipid nanoparticles (SLNs). The efficacy of PDT was estimated using the 1,3-diphenylisobenzofuran (DPBF) assay and photocytotoxicity tests on the HeLa (human cervical carcinoma) and A549 (human lung carcinoma) cell lines. The P18 N PI ME-loaded SLNs demonstrated particle sizes in the range of 158.59 nm to 248.43 nm and zeta potentials in the range of -15.97 mV to -28.73 mV. These SLNs exhibited sustained release of P18 N PI ME. DPBF analysis revealed enhanced PDT effects with SLNs containing P18 N PI ME compared with standalone P18 N PI MEs. Photocytotoxicity assays indicated toxicity under light irradiation but no toxicity in the dark. Furthermore, the smallest-sized formulation exhibited the most effective photodynamic activity. These findings indicate the potential of P18 N PI ME-loaded SLNs as promising strategies for PDT in cancer therapy.

Real time monitoring of heavy metal adulteration in biodiesel using Arduino UNO platform@A promising multi-purpose stimuli-responsive azomethine based chemoreceptor for hierarchical tri-ionic sensing

The presence of metallic adulteration even in very trace level may lead to deleterious impact on the biodiesel quality and ultimately may be responsible for the dropping down of system efficiency, which necessitates the trace level recognition of heavy metal adulteration from biodiesel. In this context, herein using an azomethine functionalized chromogenic chemoreceptor, 1-((E)-(4-hydroxyphenylimino) methyl) napthalen-2-ol (HMN) has been reported for the selective chemodosimetric recognition of Cu2+ with a lower detection threshold of 7.8 ppb via distinct chromogenic variation of HMN. In addition to this, it has also exhibited selective and reversible naked eye chromogenic sensing behaviour towards F− (LOD=160 ppb) and Al3+ (LOD=48 ppb) at very trace level, which is quite lower than the WHO permissible limit. Distinct chromogenic recognition of F− by HMN proceeds via strong intermolecular hydrogen bonding mediated improved intramolecular charge transfer. The spectroscopic response of HMN in alternate presence and absence of the targeted analytes made it suitable to formulate AND-NOT-XNOR-NAND-OR gate based ‘Castle-like’ complicated logic circuitry. In-vitro cell imaging study using A549, human lung carcinoma cell line attests intracellular recognition capability of HMN, demonstrating its effectual bio-medicinal applications. Interestingly, inspired by the capability of HMN towards recognition of copper from biodiesel specimen, an RGB-assisted device comprised of TCS color sensor and an Arduino UNO 8-bit microcontroller has been developed for real-time quantitative analysis of the biodiesel adulteration. Going one step further, utilization of lab-on-a-box based prototype to monitor the concentration-dependent chromogenic fluctuation via RGB analysis is undoubtedly beneficial for the determination of copper adulteration in biodiesel sample. The presently developed chemoreceptor can thus be regarded as a valuable addition in the field of supramolecular chemistry as well as a significant initiative towards regular monitoring of the biodiesel quality control parameters as a part of sustainable environment.

Stable Cyclometallated Palladium Complexes of Arylamides: Synthesis, Redox and Anticancer Activities

AbstractAir‐stable cyclometalated palladium(II) complexes with benzamide ligands were synthesized in high yields and characterized by X‐ray diffraction analysis, CVA, 1H NMR, 13C NMR spectroscopy, MALDI‐MS, and ESI‐MS. The electrochemical oxidation of the complexes is reversible in the presence of a quinoline substituent in the ligand and gives Pd (III) species that do not undergo reductive elimination and are detectable by ESR spectroscopy. The complexes showed high cytotoxicity against cervical cancer (M‐HeLa) and duodenal adenocarcinoma (HuTu 80), a human mammary ductal adenocarcinoma line (MCF‐7) and a human lung carcinoma cell line (A549). The possibility of generating reactive oxygen species in solution (such as OH−radicals), which can be responsible for the antitumor activity of the studied complexes, using the ESR method was shown.

Role of Ciminalum-4-thiazolidinone Hybrids in Molecular NF-κB Dependent Pathways.

A range of hybrid molecules incorporating the ciminalum moiety in the thiazolidinone ring demonstrate significant anticancer and antimicrobial properties. Therefore, the aim of our study was to evaluate the properties and mechanism of action of two 4-thiazolidinone-based derivatives, i.e., 3-{5-[(Z,2Z)-2-chloro-3-(4-nitrophenyl)-2-propenylidene]-4-oxo-2-thioxothiazolidin-3-yl}propanoic acid (Les-45) and 5-[2-chloro-3-(4-nitrophenyl)-2-propenylidene]-2-(3-hydroxyphenylamino)thiazol-4(5H)-one (Les-247). In our study, we analyzed the impact of Les-45 and Les-247 on metabolic activity, caspase-3 activity, and the expression of genes and proteins related to inflammatory and antioxidant defenses and cytoskeleton rearrangement in healthy human fibroblasts (BJ) and a human lung carcinoma cell line (A549). The cells were exposed to increasing concentrations (1 nM to 100 μM) of the studied compounds for 24 h and 48 h. A decrease in the metabolic activity in the BJ and A549 cell lines was induced by both compounds at a concentration range from 10 to 100 µM. Both compounds decreased the mRNA expression of NRF2 (nuclear factor erythroid 2-related factor 2) and β-actin in the BJ cells. Interestingly, a significant decrease in the level of NF-κB gene and protein expression was detected in the BJ cell line, suggesting a direct impact of the studied compounds on the inhibition of inflammation. However, more studies are needed due to the ability of Les-45 and Les-247 to interfere with the tubulin/actin cytoskeleton, i.e., a critical system existing in eukaryotic cells.

Antimicrobial efficacy of select medicinal plant extracts from Bangladesh against food‐borne bacterial pathogens

AbstractWe assessed the antimicrobial activity of extracts prepared with four solvents (hexane, acetone, ethanol, water) from 45 medicinal plants used in Bangladesh. Food pathogenic bacteria (Gram‐positive: Bacillus cereus, Listeria innocua, Streptococcus faecalis, and Gram‐negative: Escherichia coli, Pseudomonas aeruginosa, Salmonella enterica, and Shigella sonnei) were tested using a broth microdilution method. The extraction yield was highest (26%) for the water extract of Carica papaya and lowest (0.4%) for the acetone extract of Cynodon dactylon. In general, acetone extracts exhibited much more antibacterial activity than those obtained with the other three solvents (hexane, ethanol, and water). Gram‐positive bacteria were more sensitive than Gram‐negatives. Streptococcus faecalis was the most susceptible to inhibition by examined extracts, whereas E. coli and P. aeruginosa were the most resistant. Most inhibitory concentration‐50 (IC50) values ranged between 101 and 500 μg/mL (64 extracts, 35.5%), followed by the range of 501–1000 μg/mL (40 extracts, 22.2%). Based on IC50, the most effective plants were three species of Piper (Piper nigrum, Piper betle, and Piper chaba), followed by Nigella sativa, Psidium guajava, Syzygium cumini, C. dactylon, and Phyllanthus emblica. In addition, the toxicity of chosen extracts against normal and malignant cell lines was tested; the most effective extracts were toxic against the human lung carcinoma cell line A549, but less toxic against the human Caucasian foetal lung cell line WI26VA4. These findings suggest that some plant extracts could be employed to treat food‐borne bacterial infections, or as herbal preservatives in the food sector.

Inhibition of SARS-CoV-2 Nsp9 ssDNA-Binding Activity and Cytotoxic Effects on H838, H1975, and A549 Human Non-Small Cell Lung Cancer Cells: Exploring the Potential of Nepenthes miranda Leaf Extract for Pulmonary Disease Treatment.

Carnivorous pitcher plants from the genus Nepenthes are renowned for their ethnobotanical uses. This research explores the therapeutic potential of Nepenthes miranda leaf extract against nonstructural protein 9 (Nsp9) of SARS-CoV-2 and in treating human non-small cell lung carcinoma (NSCLC) cell lines. Nsp9, essential for SARS-CoV-2 RNA replication, was expressed and purified, and its interaction with ssDNA was assessed. Initial tests with myricetin and oridonin, known for targeting ssDNA-binding proteins and Nsp9, respectively, did not inhibit the ssDNA-binding activity of Nsp9. Subsequent screenings of various N. miranda extracts identified those using acetone, methanol, and ethanol as particularly effective in disrupting Nsp9's ssDNA-binding activity, as evidenced by electrophoretic mobility shift assays. Molecular docking studies highlighted stigmast-5-en-3-ol and lupenone, major components in the leaf extract of N. miranda, as potential inhibitors. The cytotoxic properties of N. miranda leaf extract were examined across NSCLC lines H1975, A549, and H838, focusing on cell survival, apoptosis, and migration. Results showed a dose-dependent cytotoxic effect in the following order: H1975 > A549 > H838 cells, indicating specificity. Enhanced anticancer effects were observed when the extract was combined with afatinib, suggesting synergistic interactions. Flow cytometry indicated that N. miranda leaf extract could induce G2 cell cycle arrest in H1975 cells, potentially inhibiting cancer cell proliferation. Gas chromatography-mass spectrometry (GC-MS) enabled the tentative identification of the 19 most abundant compounds in the leaf extract of N. miranda. These outcomes underscore the dual utility of N. miranda leaf extract in potentially managing SARS-CoV-2 infection through Nsp9 inhibition and offering anticancer benefits against lung carcinoma. These results significantly broaden the potential medical applications of N. miranda leaf extract, suggesting its use not only in traditional remedies but also as a prospective treatment for pulmonary diseases. Overall, our findings position the leaf extract of N. miranda as a promising source of natural compounds for anticancer therapeutics and antiviral therapies, warranting further investigation into its molecular mechanisms and potential clinical applications.

PAS-004: A novel macrocyclic MEK inhibitor to inhibit cancer cell growth in vitro and tumor growth in mouse xenograft studies.

3126 Background: Three MEK inhibitors have been approved to date to treat melanomas driven by RAS pathway mutations and a 4th compound (selumetinib) is approved to treat Neurofibromatosis type 1 (NF1) in pediatric patients. PAS-004 is the first macrocyclic MEK inhibitor in development for solid tumors and NF1. Methods: Ten NRAS mutant cancer cell lines were cultured for 48 hrs in the presence of the MEK inhibitor PAS-004, trametinib, binimetinib (bini) and selumetinib (selu) and cell proliferation was assayed using a Cell Titer Glo luminescence assay. The anti-tumor activity of PAS-004 was compared with selu and bini in two mouse xenograft studies using NRAS mutant human hepatocellular carcinoma (HCC) and lung carcinoma cell lines. Dose response was assessed with treatment initiated when the tumor reached a volume of 150 mm3 and mice treated for 20 days. Body weights and tumor volumes were measured twice weekly. Tumors were excised at the end of the study and pERK inhibition was assessed by Western blot. Terminal plasma was collected for PK analysis. Results: PAS-004 strongly inhibited 5/10 NRAS mutant cancer lines with IC50 values ranging from 0.024 to 0.306 µM. Maximal growth inhibition of >50% was achieved by PAS-004 in 8 cell lines and PAS-004 achieved greater maximal inhibition in 7/10 lines vs selu and bini. PAS-004 inhibition was comparable to trametinib in 5/10 cell lines tested. However, in contrast to trametinib PAS-004 did not reach a plateau at the highest dose tested in three of these lines. In the HCC xenograft study the highest dose of PAS-004 completely prevented tumor growth and the same dose caused a 69% reduction in tumor volume in the lung carcinoma xenograft study. The anti-tumor efficacy of PAS-004, when taken at equivalent doses, was shown to be superior to that of bini and selu. Specifically, PAS-004 at dose levels of 10 mg/kg and 5 mg/kg, once daily, exhibited higher efficacy compared to bini and selu at dose levels of 5 mg/kg and 2.5 mg/kg, when administered twice daily, respectively. No significant differences in body weight loss were seen between the compounds. Conclusions: The novel macrocyclic MEK inhibitorPAS-004 inhibited NRAS mutant tumor growth in mouse xenograft studies with similar activity as the approved MEK inhibitors selu and bini. In vitro, PAS-004 provided greater maximal growth inhibition of NRAS lines than selu and bini. These results support investigating PAS-004 further and a clinical trial in patients with advanced solid tumors carrying RAS pathway mutations, including NRAS variants, is ongoing.

Investigation on the pharmacological profile for new synthesized bis heterocyclic analogs containing nitrogen atom as anti-cancer therapy target

Cancer is a common public health disease causing mortality worldwide. Thus, providing novel chemotherapies that tackle breast cancer is of great interest. In this investigation, novel heterocyclic compounds with pyridine, pyrimidine, and pyrazole rings 2–16 were synthesized and characterized using a variety of spectrum analyses. All synthesized compounds were evaluated for their anticancer effects on human lung carcinoma cell line (H460), human pharynx squamous cell carcinoma cell line (FaDu), and common human hepatocellular carcinoma cell line (Huh7), compounds 3 (6-ethoxy-pyridine), 8 (pyridinyl-pyrazol), 9 (pyridinyl-N, N-diacetylpyrazol), 11 (pyridinyl-N-(2,4-dinitrophenyl)pyrazole), 13 (pyridinyl-isoxazole) and 16 (pyridinyl-benzo[b][1,4]thiazepine) had the maximum anticancer activity against all examined cell lines. Based on these resultss, we are able to conclude that analoges 6-Ethoxy-pyridine 3, Pyridinyl-pyrazol 8, Pyridinyl-N-(2,4-dinitrophenyl)pyrazole 11 and Pyridinyl-benzo[b][1,4]thiazepine 16 are found to be secure and specific because their IC50 values on normal cell line are higher than their IC50 values on tested cancer cell lines.

Cytotoxicity and Apoptosis Prevailed by Tricyclohexyltin(IV) Dithiocarbamate Compounds Against Human Lung Carcinoma Cell Line (A549)

Cytotoxicity and Apoptosis Prevailed by Tricyclohexyltin(IV) Dithiocarbamate Compounds Against Human Lung Carcinoma Cell Line (A549)

Silencing RNA-Mediated Knockdown of IFITM3 Enhances Senecavirus A Replication.

Senecavirus A (SVA) is a non-enveloped, positive sense, single-stranded RNA virus that causes vesicular diseases in pigs. Interferon-induced transmembrane 3 (IFITM3) is an interferon-stimulated gene (ISG) that exhibits broad antiviral activity. We investigated the role of IFITM3 in SVA replication. Both viral protein expression and supernatant virus titer were significantly increased when endogenous IFITM3 was knocked down by approximately 80% in human non-smallcell lung carcinoma cell line (NCI-H1299) compared to silencing RNA control. Interestingly, overexpression of exogenous IFITM3 in NCI-H1299 cells also significantly enhanced viral protein expression and virus titer compared to vector control, which was positively correlated with induction of autophagy mediated by IFITM3 overexpression. Overall, our results indicate an antiviral role of endogenous IFITM3 against SVA. The exact molecular mechanisms by which endogenous IFITM3 limits SVA replication remain to be determined in future studies.

Abstract 4439: Decoding the metabolic symphony TP53 mutation-driven rewiring of cellular metabolism in non-small cell lung carcinoma

Abstract TP53 is a critical regulator of major metabolic pathways. Metabolic reprogramming is one of the "hallmarks of cancer" and drives tumorigenesis. Frequent p53mutations not only eradicate tumour suppressor capacities but also confer various activities that impact the alteration of metabolic pathways now regarded as central for tumour development and progression. We selected three hotspot mutants (R175H, R273H and R249S) and wtp53 to evaluate the effects in the human non-small cell lung carcinoma cell line (NCI-H1299). Differential expressions of p53 mutants were observed in normal and glucose/glutamine starvation. However, WTp53 expression was not found to be affected. Under both the glucose and glutamine starvation, inhibition of the cell growth and migratory potential of mutant cells was observed which was more prominent in glutamine starvation. Basal respiration and ATP production in p53-/- R273H and R249S significantly increased under glucose starvation. However, Non-mitochondrial oxygen consumption and maximal respiration were found to be decreased in all the cell lines. Importantly, the cells harbouring mutation R175H increase the glycolysis and TCA cycle. The metabolic intermediates of the urea cycle were found to be increased by nearly fourfold in R273H cells. Indicating increased utilization of the urea cycle instead of the TCA cycle, which has been known to be fueled by glutamine for anaplerosis. This study demonstrates that mutp53 influences several metabolic processes and has an influence on cancer cell aggression under starvation of main carbon sources (Glucose and Glutamine). In starved conditions, cells with p53 mutations enhance mitochondrial activity and use alternative pathways in non-small cell lung cancer cells. This might provide a foundation for the development of more effective targeted therapeutics/pharmacological approaches toward variants of mutant p53. Citation Format: Jiyauddin Khan, Asad Ur Rehman, Ankit Mathur, Naveen Kumar Bhatrajuc, Anannya Tulid, Divya Rajput, Mohammad Askandar Iqbal, Daman Saluja. Decoding the metabolic symphony TP53 mutation-driven rewiring of cellular metabolism in non-small cell lung carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4439.

In vitro EVALUATION of THE EFFECTS of POTENTIAL GSK-3β INHIBITORS TERBUTALINE and ORCIPRENALINE

Lung cancer is a type of cancer that is mostly diagnosed at an advanced stage and has a short survival time despite standard chemotherapy and targeted therapies. Terbutaline and Orciprenaline are bronchodilator agent that are potent and selective β2 receptor agonists. The purpose of this study was to investigate by continuous monitoring to assay the effects of Terbutaline and Orciprenaline on human lung carcinoma cell line. Cells were treated 1, 10, 100, 200, 400 µM concentrations with Terbutaline/Orciprenaline. MTT assay and xCELLigence real-time cell analyzer were used to determine these compounds effect on cell viability. The cell index was monitored continuously by visualizing the impedance of the E-plate wells. Because of GSK3β roles in a diverse range of cellular processes like metabolism, cell proliferation, differentiation and survival and its key position at several signaling pathways, GSK3β inhibition was investigated of these molecules. It has been determined that Terbutaline and Orciprenaline inhibits GSK-3β.
 This is the first known study to demonstrate the effects of Terbutaline and Orciprenaline on A549 and the human bronchial epithelial cell line Beas-2b in real time. In this study, it was detected that Terbutaline and especially Orciprenaline may have potential therapeutic effects in lung carcinoma.

Vincazalidine A, a unique bisindole alkaloid from Catharanthus roseus.

A new dimeric indole alkaloid, vincazalidine A consisting of an aspidosperma type and a modified iboga type with 1-azatricyclo ring system consisting of one azepane and two piperidine rings coupled with an oxazolidine ring was isolated from Catharanthus roseus, and the structure including absolute stereochemistry was elucidated on the basis of spectroscopic data as well as DP4 statistical analysis. Vincazalidine A induced G2 arrest and subsequent apoptosis in human lung carcinoma cell line, A549 cells.

New pyranopyrazole based derivatives: Design, synthesis, and biological evaluation as potential topoisomerase II inhibitors, apoptotic inducers, and antiproliferative agents

A new series of pyranopyrazole-based derivatives were designed and synthesized. The synthesized compounds were assessed for their cytotoxic efficacy against A549 human lung carcinoma and MCF-7 human breast carcinoma cell lines. Three compounds (1b, 4b, and 7b) exhibited 1.3- to 2.3-fold more antiproliferative activity than that of doxorubicin against the A549 cell line. In comparison to doxorubicin, compounds 1d and 3b were 4.1- and 1.04-fold, respectively more powerful against MCF-7 cancer cells. All the synthesized compounds were found to be more selective toward A549 cancer cells than the normal human fibroblast BJ cells. Of interest, compounds 1b and 7b exhibited promising cytotoxicity and SIs of 27.72 and 25.30, respectively, towards A549 cancer cells, higher than that of doxorubicin (SI 4.81). The most potent compounds 1b, 1d, 3b, 4b, and 7b were then subjected to in vitro Topo II inhibition assay. They showed IC50 values in the range of 2.07 to 8.86 µM. Of particular interest, compound 7b (IC50 = 2.07 µM), exhibited higher Topo II inhibitory activity than that of doxorubicin (IC50 = 2.56 µM). The significant Topo II inhibition of compound 7b was explained by molecular docking simulations into the Topo II active site. Compound 7b halted the cell cycle in the S phase in A549 cancer cells. It induced total apoptosis and necrosis of 20.73- and 4-fold, respectively, greater than the control. This evidence was supported by a 3.59-fold increase in the level of apoptotic caspase-9 and a remarkable elevation of the Bax/BCL-2 ratio. The physiochemical parameters of compound 7b were aligned with Lipinski’s rule of five.

Study of the antitumor effect of the monoclonal antibody 8D1 against the membrane-associated heat shock protein Hsp70 in vivo and in vitro

It is known that the 70 kDa heat shock protein (Hsp70) is localized on the membranes of cancer cells and can serve as a target for tumor theranostics. When developing new generation drugs, priority is given to drugs for "targeted" therapy. The most interesting and promising objects in this area of pharmacology are therapeutic antibodies that directly interact with the pathogen molecule, neutralizing its effects. The present study investigated the antitumor activity of the 8D1 monoclonal antibody, specific to the membrane-associated form of Hsp70, in an in vivo model of mouse myeloma Sp2/0. It was shown that the introduction of the antibody increased the expected lifespan of animals by approximately 20% compared to the control group. The possibility of enhancing the action of the 8D1 antibody has been demonstrated on an in vitro model of suppressing the viability of human lung carcinoma cell line A549 using a conjugate of this antibody with doxorubicin.

Green synthesis of silver nanoparticles using Justicia adhatoda leaves extract and its anticancer effect on human lung carcinoma via induced apoptosis mechanism

In this study, Justicia adhatoda leaves extract was used to synthesize silver nanoparticles (AgNPs) and assess its anticancer attributes against human lung carcinoma (A549) cell line via induction of apoptosis mechanism. Initially, the biosynthesis of AgNPs was evident by observing the appearance of dark brown colour solution. UV–Vis spectrum showed characteristic surface plasmon resonance peak at 420 nm. FT-IR spectroscopy demonstrated the presence of distinct functional groups in both the extract and AgNPs. The peaks in XRD pattern corresponded to 101, 111, 200, and 220 crystal planes, thereby representing face-centred cubic silver. The EDX analysis confirmed the reduction of silver ions. The HR-SEM revealed spherical-shaped nanoparticles with an average size of 8–13 nm. In vitro cytotoxicity of extract and AgNPs was determined against A549 cell lines using MTT assay. The AgNPs revealed higher cytotoxity (59.25 ± 1.3–5.55 ± 1.3 %) than the extract (81.48 ± 1.3–16.66 ± 1.6 %) with reduced viabilities of cells at different concentrations. The IC50 values of the extract and AgNPs were calculated as 95.36 and 15.1 µg/mL, respectively. Apoptosis of AgNPs was analyzed using varied techniques as per the standard protocols. Acridine orange staining showed reduced green fluorescence of A549 cells due to the action of AgNPs. DNA fragmentation assay revealed the breakage of DNA double strands of cells and yielded laddered pattern. Flow cytometry analysis depicted increment in the cells count in S phase and concomitant decrement in Go/G1 phase. Quantitative real-time PCR demonstrated the upregulation and downregulation of Bax and Bcl-2 genes, respectively. Additionally, the exposure of A549 cells with AgNPs induced cytochrome C production from depolarized mitochondrial membrane into cytosol, which further upregulated caspase-9 and caspase-3 genes. In conclusion, J. adhatoda leaves-mediated AgNPs induced the apoptosis mechanism in A549 lung adenocarcinoma cells and indicated its paramount role as an effectual anticancer agent in future nanomedicine.

Photoinduced cytotoxic activity of a rare ruthenium nitrosyl phenanthroline complex showing NO generation in human cells.

A new nitro-nitrosyl complex [RuNO(Phen)(NO2)2OH] (1) was synthesized and characterized by X-ray diffraction, where Phen = 1,10-phenanthroline. The complex was crystallized in two different modifications without (1) and with a solvent molecule of DMF (1a). The photolysis process together with the determination of the quantum yield of NO release was investigated in acetonitrile solution using a special flow-through system for the simultaneous registration of infrared (IR) and optical absorption (UV-vis) spectra under irradiation with 450 nm light. The quantum yield of photoinduced NO release was 4.0 ± 0.2%. DFT calculations showed that the main contribution to the absorption band at 450 nm is made by the HOMO/HOMO-1 → LUMO transitions, which are represented by the transfer of electron density from the -OH and -NO2 ligands to the orbitals located on the Ru-NO bond. The dark and photoinduced cytotoxicity of the complex was studied against the human breast adenocarcinoma (MCF-7) and lung carcinoma (A549) cell lines and human non-tumor lung fibroblasts (MRC5). The complex shows a low cytotoxicity on MCF-7 cells (ICdark50 = 90.6 ± 6.2 μM and ICirr.50 = 95.3 ± 11.4 μM) and a moderate dark cytotoxicity on A549 and MRC5 cells (ICdark50 = 33.4 ± 2.6 μM and ICdark50 = 62.6 ± 3.1 μM, respectively), which slightly increases after irradiation (ICirr.50 = 21.2 ± 3.3 μM and ICirr.50 = 47.2 ± 2.3 μM, respectively).

Long-term shelf-life liposomes for delivery of prednisolone and budesonide

Liposomes are nanoscale drug delivery systems built up from lipid layers and are able to spontaneously self-assemble in an aqueous environment. Both hydrophilic and hydrophobic drugs can be delivered by liposomes and this kind of nanoformulation offers many advantages regarding biodistribution, drug absorption and controlled drug release. Corticosteroids as lipophilic molecules are able to integrate into the lipid bilayer. This novel approach can improve the efficacy of several anti-inflammatory, such as asthma therapy.Our aim was to create liposomes with long shelf-life, which can incorporate and release corticosteroids such as Prednisolone (Pred) and Budesonide (Bud) at the temperature of inflamed tissues. Two kinds of liposome samples were prepared from three different kinds of phospholipids to get unilamellar vesicles with 100 nm in diameter and characterize their physicochemical properties and effect on living cells. Their main phase transition temperature in the physiologically relevant temperature range was measured by differential scanning calorimetry. According to the size distributions determined by dynamic light scattering, all drug-containing liposomes were stable for 6 months. All of the liposome types have a slightly negative zeta potential value. The Fourier-transform infrared spectroscopy revealed no chemical interaction between the drug and lipid molecules. The entrapment efficacy was determined by size-exclusion gel chromatography combined with UV–VIS spectrophotometry and it was very high in both cases (between 70 and 87%). The drug leakage was 35–40% for Pred and 6–8% for Bud in the first 30 min. The effect of liposomal drugs on cell viability was measured on the EBC-1 human lung carcinoma cell line. Neither the free corticosteroids nor their liposomal form were toxic to the cells. The cellular internalization of the liposomes was proved by flow cytometry and confocal microscopy.In summary, these liposomes could be useful in the delivery of corticosteroids (Pred or particularly Bud) in more effective asthma therapy, having fewer side effects due to the nanoformulation.

Design, synthesis and bioevaluation of novel prenylated chalcones derivatives as potential antitumor agents

A series of novel prenylated chalcone derivatives with broad spectrum anticancer potential were designed and synthesized. Some of the synthesized target compounds showed potent anti-proliferative activities toward LNCaP (prostate cancer cell line), K562 (human leukemia cells), A549 (human lung carcinoma cell line) and HeLa (cervical cancer cell line) cell lines. Among of the active compounds, (E)-1-(4-(2-(diethylamino)ethoxy)-2-hydroxy-6-methoxy-3-(3-methylbut-2-en-1-yl)phenyl)-3-(pyridin-3-yl)prop-2-en-1-one (C36) was directly interacted with protein kinase B (PKB), also known as AKT, significantly inhibited the pPI3K, pAKT(Ser473) protein levels to repress the growth of cancer cells by inducing apoptosis, arresting cell cycle. Our studies provide support for prenylated chalcone derivatives potential applications in cancer treatment as a potential AKT inhibitor.

LCMR1 Promotes Large-Cell Lung Cancer Proliferation and Metastasis by Downregulating HLA-Encoding Genes.

Lung cancer is notorious for its high global morbidity and mortality. Here, we examined whether the LCMR1 gene, which we previously cloned from a human large-cell lung carcinoma cell line, contributes to the proliferation and metastasis of large-cell lung carcinoma. To this end, we performed pan-cancer and non-small cell lung cancer (NSCLC) cell line-based LCMR1 expression profiling. Results revealed that LCMR1 was expressed at high levels in most solid tumors, including NSCLC. LCMR1 expression was the highest in the 95D large cell lung cancer cell line. Functional studies using lentivirus-based knockdown revealed that LCMR1 was critical for the proliferation, migration, and invasion of cultured large cell lung cancer cells. Moreover, blocking this gene significantly reduced tumor growth in a 95D cell xenograft mouse model. A multiple sequence-based assay revealed a mechanism by which LCMR1 diminished the RNA Pol II occupancy at the promoter of human leukocyte antigen (HLA)-encoding genes to prevent their transcription. The HLA genes play vital roles in cancer-specific antigen presentation and anticancer immunity. A correlation assay using TCGA database identified a negative relationship between the expression levels of LCMR1 and HLA coding genes. Taken together, our findings demonstrate that LCMR1 is required for large cell lung cancer cell growth and invasion and suggest its potential as a valid target in clinical treatment.