A549 Lung Research Articles

Comprehensive analysis of phytochemical profiling, cytotoxic and antioxidant potentials, and identification of bioactive constituents in methanoic extracts of Sonneratia apetala fruit

In the delta region of Bangladesh, Sonneratia apetala, also known as Keora and mangrove apple, is widely recognized for its dual role as a source of both food and medicine. Seasonal S. apetala fruits were gathered from Hatiya, Noakhali, in October 2021. The samples were segregated into pericarps and seeds, then fractionated into methanol segments. The anti-proliferative activities of these samples against lung A549 cells were evaluated using the Trypan blue exclusion method. Additionally, High-Performance Liquid Chromatography (HPLC) was employed to quantify phenolic compounds, while standard protocols facilitated the identification of specific phytochemical constituents. Chemical profiling via Gas Chromatography-Mass Spectrometry (GC-MS) and the isolation and detection of bioactive compounds through column chromatography and Nuclear Magnetic Resonance (NMR) analysis were undertaken. The methanol fractions of the seeds and pericarp were found to contain carbohydrates, tannins, flavonoids, steroids, alkaloids, glycosides, and terpenoids, with the absence of saponins and anthraquinones. Notably, the anti-proliferative effect demonstrated statistical significance at a concentration of 300 μg/mL for both extracts. Furthermore, HPLC analysis identified and quantified six polyphenols: catechin hydrate, (−)-epicatechin, rutin hydrate, trans-ferulic acid, trans-cinnamic acid, myricetin, and kaempferol, with the following concentrations: 46.65 and 12.72; 349.29 and 140.39; 5.26 and 33.06; 10.35 and 29.28; ND and 11.93; and 10.03 and 7.90 mg/100 g in the methanol fraction of the seed and pericarp, respectively. GC-MS analysis of S. apetala fruit revealed five notable compounds with significant peak areas (%): 2-methyltetracosane, tetratetracontane, heptacosane, 1-chloro-2-hexyl-1-octanol, and phenol, 3,5-bis(1,1-dimethylethyl), exhibiting peak areas of 43.96, 35.8, and 15.95, respectively. Meanwhile, the notable peak in S. apetala seeds was 1,3-benzenedicarboxylic acid, bis(2-ethylhexyl) ester, with a peak area (%) of 100. These compounds are known for their anticancer and antioxidant properties. Therefore, S. apetala, particularly its seeds and fruits, shows promising potential for development into dietary supplements and functional foods.

Gelatin nanoparticles loaded with 3-alkylpyridinium salt APS7, an analog of marine toxin, are a promising support in human lung cancer therapy

This study demonstrates the potential of gelatin nanoparticles as a nanodelivery system for antagonists of nicotinic acetylcholine receptors (nAChRs) to improve chemotherapy efficacy and reduce off-target effects. Too often, chemotherapy for lung cancer does not lead to satisfactory results. Therefore, new approaches directed at multiple pharmacological targets in cancer therapy are being developed. Following the activation of nAChRs (e.g. by nicotine), cancer cells begin to proliferate and become more resistant to chemotherapy-induced apoptosis. This work shows that the 3-alkylpyridinium salt, APS7, a synthetic analog of a toxin from the marine sponge Haliclona (Rhizoneira) sarai, acts as an nAChR antagonist that inhibits the pro-proliferative and anti-apoptotic effects of nicotine on A549 human lung adenocarcinoma cells. In this study, gelatin-based nanoparticles filled with APS7 (APS7-GNPs) were prepared and their effects on A549 cells were compared with that of free APS7. Both APS7 and APS7-GNPs inhibited Ca2+ influx and increased the efficacy of cisplatin chemotherapy in nicotine-stimulated A549 cells. However, significant benefits from APS7-GNPs were observed – a stronger reduction in the proliferation of A549 lung cancer cells and a much higher selectivity in cytotoxicity towards cancer cells compared with non-tumorigenic lung epithelial BEAS-2B cells.

Increased [18F]FDG uptake of radiation-induced giant cells: a single-cell study in lung cancer models

Positron emission tomography (PET), a cornerstone in cancer diagnosis and treatment monitoring, relies on the enhanced uptake of fluorodeoxyglucose ([18F]FDG) by cancer cells to highlight tumors and other malignancies. While instrumental in the clinical setting, the accuracy of [18F]FDG-PET is susceptible to metabolic changes introduced by radiation therapy. Specifically, radiation induces the formation of giant cells, whose metabolic characteristics and [18F]FDG uptake patterns are not fully understood. Through a novel single-cell gamma counting methodology, we characterized the [18F]FDG uptake of giant A549 and H1299 lung cancer cells that were induced by radiation, and found it to be considerably higher than that of their non-giant counterparts. This observation was further validated in tumor-bearing mice, which similarly demonstrated increased [18F]FDG uptake in radiation-induced giant cells. These findings underscore the metabolic implications of radiation-induced giant cells, as their enhanced [18F]FDG uptake could potentially obfuscate the interpretation of [18F]FDG-PET scans in patients who have recently undergone radiation therapy.

3,5-DCQA as a Major Molecule in MeJA-Treated Dendropanax morbifera Adventitious Root to Promote Anti-Lung Cancer and Anti-Inflammatory Activities.

(1) Background: Phytochemicals are crucial antioxidants that play a significant role in preventing cancer. (2) Methods: We explored the use of methyl jasmonate (MeJA) in the in vitro cultivation of D. morbifera adventitious roots (DMAR) and evaluated its impact on secondary metabolite production in DMAR, optimizing concentration and exposure time for cost-effectiveness. We also assessed its anti-inflammatory and anti-lung cancer activities and related gene expression levels. (3) Results: MeJA treatment significantly increased the production of the phenolic compound 3,5-Di-caffeoylquinic acid (3,5-DCQA). The maximum 3,5-DCQA production was achieved with a MeJA treatment at 40 µM for 36 h. MeJA-DMARE displayed exceptional anti-inflammatory activity by inhibiting the production of nitric oxide (NO) and reactive oxygen species (ROS) in LPS-induced RAW 264.7 cells. Moreover, it downregulated the mRNA expression of key inflammation-related cytokines. Additionally, MeJA-DMARE exhibited anti-lung cancer activity by promoting ROS production in A549 lung cancer cells and inhibiting its migration. It also modulated apoptosis in lung cancer cells via the Bcl-2 and p38 MAPK pathways. (4) Conclusions: MeJA-treated DMARE with increased 3,5-DCQA production holds significant promise as a sustainable and novel material for pharmaceutical applications thanks to its potent antioxidant, anti-inflammatory, and anti-lung cancer properties.

In silico investigation and biological evaluation viz antimicrobial, genotoxic, and anticancer potentials of new dihydropyrimidinones (DHPMs) synthesized by Biginelli reaction

Dihydropyrimidin-2(1H)-ones (DHPMs) are attracting growing interest in synthetic and medical organic chemistry due to their biological and therapeutic potential. In this study, we synthesized DHPM derivatives via the Biginelli reaction from bisdialdehyde to identify lead compounds. Using SWISSADME analysis, we assessed druglikeness features of the DHPM derivatives. Antimicrobial properties, including antibacterial and antifungal activities, were evaluated, and promising compounds were tested for their ability to inhibit A549 lung cancer cell growth. Thin-layer chromatography confirmed product formation, while spectroscopic methods characterized the structures. Lipophilicity values indicated strong oral absorption potential. In vitro drug release and cell viability studies were conducted. DHPMs 7, 8, and B1 exhibited broad-spectrum antimicrobial activity. Molecular docking revealed DHPM 2′s potential in cancer treatment via effective binding with VEGFR-2 kinase. Genotoxic and anticancer activities were assessed, with DHPM 8 showing promising action against dangerous bacteria and fungi. Further research is warranted to explore therapeutic applications of these compounds.

The Influence of the Auxiliary Ligand in Monofunctional Pt(II) Anticancer Complexes on the DNA Backbone.

Monofunctional platinum complexes offer a promising alternative to cisplatin in cancer chemotherapy, showing a unique mechanism of action. Their ability to induce minor helix distortions effectively inhibits DNA transcription. In our study, we synthesized and characterized three monofunctional Pt(II) complexes with the general formula [Pt(en)(L)Cl]NO3, where en = ethylenediamine, and L = pyridine (py), 2-methylpyridine (2-mepy), and 2-phenylpyridine (2-phpy). The hydrolysis rates of [Pt(en)(py)Cl]NO3 (1) and [Pt(en)(2-mepy)Cl]NO3 (2) decrease with the bulkiness of the auxiliary ligand with k(1) = 2.28 ± 0.15 × 10-4 s-1 and k(2) = 8.69 ± 0.98 × 10-5 s-1 at 298 K. The complex [Pt(en)(2-phpy)Cl]Cl (3) demonstrated distinct behavior. Upon hydrolysis, an equilibrium (Keq = 0.385 mM) between the complexes [Pt(en)(2-phpy)Cl]+ and [Pt(en)(2-phpy-H+)]+ was observed with no evidence (NMR or HR-ESI-MS) for the presence of the aquated complex [Pt(en)(2-phpy)(H2O)]2+. Despite the kinetic similarities between phenanthriplatin and (2), complexes (1) and (2) exhibit minimal activity against A549 lung cancer cell line (IC50 > 100 μΜ), whereas complex (3) exhibits notable cytotoxicity (IC50 = 41.11 ± 2.1 μΜ). In examining the DNA binding of (1) and (2) to the DNA model guanosine (guo), we validated their binding through guoN7, which led to an increased population of the C3'-endo sugar conformation, as expected. However, we observed that the rapid transition 2E (C2'-endo) ↔ 3E (C3'-endo), in the case of [Pt(en)(py)(guo)](NO3)2 ([1-guo]), slows down in the case of [Pt(en)(2-mepy)(guo)](NO3)2 ([2-guo]), resulting in separate signals for the two conformers in the 1H NMR spectra. This phenomenon arises from the steric hindrance between the methyl group of pyridine and the sugar moiety of guanosine. Notably, this hindrance is absent in [2-(9-MeG)] (9-MeG = 9-methylguanine), probably due to the absence of a bulky sugar unit in 9-MeG. In the case of (3), where the bulkiness of the substitution on the pyridine is further increased by a phenyl group, we observed a notable proximity between 9-MeGH8 and the phenyl ring of 2-phpy. Considering that only (3) exhibited good cytotoxicity against the A549 cancer cell line, it is suggested that auxiliary ligands, L, with an extended aromatic system and proper orientation in complexes of the type cis-[Pt(en)(L)Cl]NO3, may enhance the cytotoxic activity of such complexes.

Thyroid hormone enhances efficacy of cisplatin in lung cancer patients via down-regulating GLUT1 expression and reversing the Warburg effect

Cisplatin (CDDP) is a standard non-small cell lung cancer (NSCLC) chemotherapy, but its efficacy is hampered by resistance, partly due to the Warburg effect. This study investigates how thyroid hormones enhance the Warburg effect, increasing sensitivity to cisplatin in lung cancer. Clinical data from advanced NSCLC patients were analyzed based on thyroid hormone levels, categorizing patients into high and low groups. Cellular experiments involved Control, 10uM CDDP, 10uM CDDP + 0.1uM T3, and 10uM CDDP + 0.1uM T4 categories. Parameters were measured in A549 and PC9 lung cancer cells, including proliferation, apoptosis, mitochondrial membrane potential, ROS production, glycolysis enzyme activity, lactic acid level, and ATP content. Gene and protein expressions were assessed using qPCR and Western Blot. Analysis revealed higher FT3 levels correlated with prolonged progression-free survival before chemotherapy (median PFS: high FT3 group = 12.67 months, low FT3 group = 7.03 months, p = 0.01). Cellular experiments demonstrated that thyroid hormones increase lung cancer cell sensitivity to cisplatin, inhibiting proliferation and enhancing efficacy. The mechanism involves thyroid hormones and cisplatin jointly down-regulating MSI1/AKT/GLUT1 expression, reducing lactic acid and glycolysis. This Warburg effect reversal boosts ATP levels, elevates ROS, and decreases MMP, enhancing cisplatin effectiveness in A549 and PC9 cells. In conclusion, elevated free T3 levels in advanced NSCLC patients correlate with prolonged progression-free survival under cisplatin chemotherapy. Cellular experiments reveal that thyroid hormones enhance lung cancer cell sensitivity to cisplatin by reversing the Warburg effect, providing a mechanistic basis for improved therapeutic outcomes.

Diallyl disulfide, the bioactive component of Allium species, ameliorates pulmonary fibrosis by mediating the crosstalk of farnesoid X receptor and yes-associated protein 1 signaling pathway.

Environmental pollution, virus infection, allergens, and other factors may cause respiratory disease, which could be improved by dietary therapy. Allium species are common daily food seasoning and have high nutritional and medical value. Diallyl disulfide (DADS) is the major volatile oil compound of Allium species. The present study aims to explore the preventive effect and potential mechanism of DADS on pulmonary fibrosis. C57BL/6J mice were intratracheally injected with bleomycin (BLM) to establish pulmonary fibrosis and then administrated with DADS. Primary lung fibroblasts or A549 were stimulated with BLM, followed by DADS, farnesoid X receptor (FXR) agonist (GW4064), yes-associated protein 1 (YAP1) inhibitor (verteporfin), or silencing of FXR and YAP1. In BLM-stimulated mice, DADS significantly ameliorated histopathological changes and interleukin-1β levels in bronchoalveolar lavage fluid. DADS decreased fibrosis markers, HIF-1α, inflammatory cytokines, and epithelial-mesenchymal transition in pulmonary mice and activated fibroblasts. DADS significantly enhanced FXR expression and inhibited YAP1 activation, which functions as GW4064 and verteporfin. A deficiency of FXR or YAP1 could result in the increase of these two protein expressions, respectively. DADS ameliorated extracellular matrix deposition, hypoxia, epithelial-mesenchymal transition, and inflammation in FXR or YAP1 knockdown A549. Taken together, targeting the crosstalk of FXR and YAP1 might be the potential mechanism for DADS against pulmonary fibrosis. DADS can serve as a potential candidate or dietary nutraceutical supplement for the treatment of pulmonary fibrosis.

N-Hydroxyalkanamide Based Organo/hydrogels as Novel Scaffolds for pH-Dependent Metronidazole and Theophylline Release.

The traditional delivery of metronidazole and theophylline presents challenges like bitter taste, variable absorption, and side effects. However, gel-based systems offer advantages including enhanced targeted drug delivery, minimized side effects, and improved patient compliance, effectively addressing these challenges. Consequently, a cost-effective synthesis of N-hydroxyalkanamide gelators with varying alkyl chain lengths was achieved in a single-step reaction procedure. These gelators formed self-assembled aggregates in DMSO/water solvent system, resulting in organo/hydrogels at a minimum gelation concentration of 1.5 % w/v. Subsequently, metronidazole and theophylline were encapsulated within the gel core and released through gel-to-sol transition triggered by pH variation at 37 °C, while maintaining the structural-activity relationship. UV-vis spectroscopy was employed to observe the drug release behavior. Furthermore, in vitro cytotoxicity assays revealed cytotoxic effects against A549 lung adenocarcinoma cells, indicating anti-proliferative activity against human lung cancer cells. Specifically, the gel containing theophylline (16HAD+Th) exhibited cytotoxicity on cancerous A549 cells with IC50 values of 19.23±0.6 μg/mL, followed by the gel containing metronidazole (16HAD+Mz) with IC50 values of 23.75±0.7 μg/mL. Moreover, the system demonstrated comparable antibacterial activity against both gram-negative (E. coli) and gram-positive bacteria (S. aureus).

Abstract A004: Radiotherapy sensitizes preclinical models to DNA damage response agents

Abstract Introduction Radiotherapy is a key treatment for various cancers, with nearly 50% of all cancer patients receiving it as part of their therapeutic plan. It can activate cytotoxic signaling pathways to promote cancer cell death but also trigger cytoprotective mechanisms that respond to cellular damage. These cytoprotective mechanisms can be inhibited by targeted anticancer agents such as DNA damage response (DDR) agents, suggesting that radiotherapy could enhance the efficacy of these drugs. This study presents data showing radiotherapy enhances the potency of DDR agents in preclinical models. Methods and experimental procedures The MDA-MB-436 breast and A549 lung cancer cell lines were utilized to establish in vitro assays and in vivo models for the study. Agents targeting DNA-PK (AZD7648) and PARP (niraparib) were used as they work on pathways crucial for the repair of radiation-induced DNA double-strand breaks. The effects on cell viability and DDR biomarkers were assessed after treatment with irradiation (IR), compound or in combination both in vitro and in vivo. Targeted X-rays were delivered using an Xstrahl CIX3 cabinet irradiator, in vivo radiotherapy was delivered to the tumor only. Data An increased sensitivity to DDR agents when combined with radiotherapy was observed in vitro in both cell lines, compared to standalone treatments. A single dose of radiotherapy significantly reduced cell viability beyond the effects of radiotherapy or compound treatment alone. The induction of biomarkers by radiotherapy as monotherapy or in combination with DDR inhibitors was assessed. Changes in biomarker expression were consistent with those observed in the in vivo xenograft models. The administration of fractionated dosing regimens for radiotherapy was well-tolerated in vivo. Combination of radiotherapy with the DDR compounds led to tumor growth delay and enhanced survival outcomes. Conclusion In summary, in vitro assays and in vivo models have been established to investigate the synergistic effects of the combination of radiotherapy and DDR agents. Radiotherapy increased sensitivity of 2 human cancer cell lines to the DDR agents in vitro, and lead to tumor growth delay in vivo. These assays can be used as preclinical tools to identify novel compounds or mechanisms that can be successfully combined with radiotherapy. Citation Format: Pablo Binder, Theoni Katopodi, Lyndsey Hanson, Charlotte R. Bell, Eimear Flanagan, Paul Farrington, Nick Moore, Emily Wright, Yin Xin Ho, Tobias Bunday, Stewart Brown, Amy Cantrell, Yael Mamane, Jon Greenall, Shannon Sharman, John Woolley, Lorraine M. Mooney, Jane Kendrew. Radiotherapy sensitizes preclinical models to DNA damage response agents [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Expanding and Translating Cancer Synthetic Vulnerabilities; 2024 Jun 10-13; Montreal, Quebec, Canada. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(6 Suppl):Abstract nr A004.

Apoptosis inducing anti-proliferative activity of Citrullus lanatus seeds against A549 cell lines

Cancer is a leading dangerous death-causing disease in millions over the world. It arises due to the uncontrolled growth of mal-functioned cells and formed as tumors. The disease can affect any part of the body. Still, it is a quest to find anti-cancer drugs which has been the major research endeavor around the globe. Traditionally humans use plants and their derived products as a source to cure various diseases. In recent years many researches had paved the way to use plant-based drugs. The current research aims to evaluate the anticancer activity of Citrullus lanatus seeds against A549 lung carcinoma epithelial cell lines. The study uses C. lanatus seeds which naturally contains antioxidants and phytochemicals that prevent cancer cell proliferation. The ethanolic seed extract of C. lanatus showed the presence of phytochemicals such as saponins, alkaloids, proteins and flavonoids by preliminary screening. The extract was tested for its anti-inflammatory showing 96.16 % at maximum concentration. The microbial assays also showed good signs of inhibition against the microorganisms by forming a zone of inhibition. The safety and efficacy of the extract were determined by MTT assay for the cytotoxicity using A549 cancer cell lines and non-cancerous cell lines. The IC50 concentration of C. lanatus seed extract showed dosage dependently at 51.73 μg/ml for A549 cell lines. They also resulted in significant induced cell cycle arrest and apoptosis at the G2 phase by inhibiting the A549 cell line proliferation. The present study works on lung carcinoma to find a better procurement in a traditional way that can develop future hope in the pharmaceutical industry.

Salvianolic acid B inhibits the growth and metastasis of A549 lung cancer cells through the NDRG2/PTEN pathway by inducing oxidative stress.

Salvianolic acid B (Sal B) has demonstrated anticancer activity against various types of cancer. However, the underlying mechanism of Sal B-mediated anticancer effects remains incompletely understood. This study aims to investigate the impact of Sal B on the growth and metastasis of human A549 lung cells, as well as elucidate its potential mechanisms. In this study, different concentrations of Sal B were administered to A549 cells. The effects on migration and invasion abilities were assessed using MTT, wound healing, and transwell assays. Flow cytometry analysis was employed to evaluate Sal B-induced apoptosis in A549 cells. Western blotting and immunohistochemistry were conducted to measure the expression levels of cleaved caspase-3, cleaved PARP, and E-cadherin. Commercial kits were utilized for detecting intracellular reactive oxygen species (ROS) and NAD+. Additionally, a xenograft model with transplanted A549 tumors was employed to assess the anti-tumor effect of Sal B in vivo. The expression levels of NDRG2, p-PTEN, and p-AKT were determined through western blotting. Our findings demonstrate that Sal B effectively inhibits proliferation, migration, and invasion in A549 cells while inducing dose-dependent apoptosis. These apoptotic responses and inhibition of tumor cell metastasis are accompanied by alterations in intracellular ROS levels and NAD+/NADH ratio. Furthermore, our in vivo experiment reveals that Sal B significantly suppresses A549 tumor growth compared to an untreated control group while promoting increased cleavage of caspase-3 and PARP. Importantly, we observe that Sal B upregulates NDRG2 expression while downregulating p-PTEN and p-AKT expressions. Collectively, our results provide compelling evidence supporting the ability of Sal B to inhibit both growth and metastasis in A549 lung cancer cells through oxidative stress modulation as well as involvement of the NDRG2/PTEN/AKT pathway.

Design, synthesis and apoptotic activity of substituted chalcones tethered 1,3,5-triazine hybrids: An insights from molecular docking, molecular dynamics simulations, DFT, ADME, and DAPI analyses

A novel library of chalcone tethered 1,3,5-triazine hybrids (5a-j) were designed and synthesized and their structures were confirmed by using spectroscopic/analytical techniques. The anticancer activity of the synthesized novel derivatives (5a-j) was evaluated against four human cancer cell lines: PC3 (Prostate cancer), A549 (Lung cancer), MCF7 (Breast cancer), and Colo-205 (Colon cancer) by employing of MTT assay method. In comparison to “Etoposide”, all the compounds showed excellent to moderate activity. The IC50 values of the novel derivatives (5a-j) ranged from 0.01±0.0032 µM to 12.4 ± 6.18 µM whereas positive control (Etoposide) showed 0.14±0.017 µM to 3.08±0.135 µM respectively. The newly developed substituted chalcone linked triazine hybrids were found to be good alternative anticancer agents. Among the all, (5a-j), mainly 5a, 5e, 5f, 5 g and 5j displayed highly potent anticancer activity towards MCF7 (5a), A549 (5 g), PC3 (5e, 5f) and Colo-205 (5j) human cancer cell lines. Principally, two compounds 5a and 5e were displayed as the most promising activities. The apoptotic mechanism in anticancer activity was further confirmed by nuclear staining analysis on more active test compounds 5a and 5e by DAPI (4′,6-diamidino-2-phenylindole) at different concentrations with MCF-7 cells, Additionally, all the synthesized compounds were investigated by molecular docking simulation studies with topoisomerase-IIβ enzyme (PDB ID: 3QX3) protein to correlate the in-vitro biological activity data evaluated on four human cancer cell lines. The docking scores of the newly produced conjugates (5a-j) varied from – 7.52 kcal/mol to -6.27 kcal/mol, indicating these compounds serve as an inhibitor. Human oral absorption is expected to be greater than 75 %. The in-vitro cytotoxicity behavior of tested compounds was further supported by in-silico predictions such as ADME, MD simulations and DFT studies.

Investigation of Lung Cancer Cell Response to Cryoablation and Adjunctive Gemcitabine-Based Cryo-Chemotherapy Using the A549 Cell Line.

Due to the rising annual incidence of lung cancer (LC), new treatment strategies are needed. While various options exist, many, if not all, remain suboptimal. Several studies have shown cryoablation to be a promising approach. Yet, a lack of basic information pertaining to LC response to freezing and requirement for percutaneous access has limited clinical use. In this study, we investigated the A549 lung carcinoma cell line response to freezing. The data show that a single 5 min freeze to -15 °C did not affect cell viability, whereas -20 °C and -25 °C result in a significant reduction in viability 1 day post freeze to <10%. These populations, however, were able to recover in culture. Application of a repeat (double) freeze resulted in complete cell death at -25 °C. Studies investigating the impact of adjunctive gemcitabine (75 nM) pretreatment in combination with freezing were then conducted. Exposure to gemcitabine alone resulted in minimal cell death. The combination of gemcitabine pretreatment and a -20 °C single freeze as well as combination treatment with a -15 °C repeat freeze both resulted in complete cell death. This suggests that gemcitabine pretreatment may be synergistically effective when combined with freezing. Studies into the modes of cell death associated with the increased cell death revealed the increased involvement of necroptosis in combination treatment. In summary, these results suggest that repeat freezing to -20 °C to -25 °C results in a high degree of LC destruction. Further, the data suggest that the combination of gemcitabine pretreatment and freezing resulted in a shift of the minimum lethal temperature for LC from -25 °C to -15 °C. These findings, in combination with previous reports, suggest that cryoablation alone or in combination with chemotherapy may provide an improved path for the treatment of LC.

Construction of a Synergy Combination Model for Turmeric (Curcuma longa L.) and Black Pepper (Piper nigrum L.) Extracts: Enhanced Anticancer Activity against A549 and NCI-H292 Human Lung Cancer Cells.

Extensive research on medicinal herbs for bioactive compounds proposes that they could replace synthetic drugs, reducing side effects and economic burdens. Especially, interest in the synergistic benefits of natural products is increasing, implying that their combined use may enhance therapeutic effectiveness. This study aimed to explore the synergetic effects of turmeric (Curcuma longa L.) and black pepper (Piper nigrum L.) extract on lung normal (MRC-5) and cancer (A549 and NCI-H292) cell lines. The turmeric extract (TM) only affected the lung cancer cell lines, but it had no impact on the MRC-5 cell line. On the other hand, the black pepper extract (BP) did not cause any damage to either the lung normal or cancer cell lines, even at concentrations of up to 400 µg/mL. Response surface methodology was used to predict the ideal synergistic concentrations (EC50) of TM and BP, which were found to be 48.5 and 241.7 µg/mL, respectively. Notably, the selected condition resulted in higher cytotoxicity compared to the exposure to TM alone, indicating a potent synergetic effect. The rate of curcumin degradation under this combined treatment was significantly decreased to 49.72 ± 5.00 nmol/h/µg for A549 cells and 47.53 ± 4.78 nmol/h/µg for NCI-H292 cells, respectively, as compared to curcumin alone. Taken together, this study confirmed the potent synergistic effect of TM and BP on lung cancer cell lines. Further research is required to identify their specific synergetic mechanisms. Our findings provide crucial foundational data on the synergistic effects of TM and BP.

1,3-Diaryl Triazenes Incorporating Disulfonamides Show Both Antiproliferative Activity and Effective Inhibition of Tumor-associated Carbonic Anhydrases IX and XII.

The aim of this study was to synthesize a library of novel di-sulfa drugs containing 1,3- diaryltriazene derivatives TS (1-13) by conjugation of diazonium salts of primary sulfonamides with sulfa drugs to investigate the cytotoxic effect of these new compounds in different cancer types and to determine their inhibitory activity against tumor-associated carbonic anhydrases IX and XII. A carbonic anhydrase inhibitory activity of the obtained compounds was evaluated against four selected human carbonic anhydrase isoforms (hCA I, hCA II, hCA IX and hCA XII) by a stoppedflow CO2 hydrase assay. In addition, in vitro, cytotoxicity studies were applied by using A549 (lung cancer), BEAS-2B (normal lung), MCF-7 (breast cancer), MDA-MB-231 (breast cancer), CRL-4010 (normal breast epithelium), HT-29 (colon cancer), and HCT -116 (colon cancer) cell lines. As a result of the inhibition data, the 4-aminobenzenesulfonamide derivatives were more active than their 3-aminobenzenesulfonamide counterparts. More specifically, compounds TS-1 and TS-2, both of which have primary sulfonamides on both sides of the triazene linker, showed the best inhibitory activity against hCA IX with Ki values of 19.5 and 13.7 nM and also against hCA XII with Ki values of 6.6 and 8.3 nM, respectively. In addition, in vitro cytotoxic activity on the human breast cancer cell line MCF-7 showed that some derivatives of di-sulfa triazenes, such as TS-5 and TS-13, were more active than SLC-0111. With the aim of developing more potent and isoform-selective CA inhibitors, these novel hybrid molecules containing sulfa drugs, triazene linkers, and the classical primary sulfonamide chemotype may be considered an interesting example of effective enzyme inhibitors and important anticancer agents.

Discovery of Substituted 2-oxoquinolinylthiazolidin-4-one Analogues as Potential EGFRK Inhibitors in Lung Cancer Treatment.

Cancer is the second leading cause of death globally and is responsible for an estimated 9.6 million deaths in 2018. Globally, about 1 in 6 deaths is due to cancer and the chemotherapeutic drugs available have high toxicity and have reported side effects hence, there is a need for the synthesis of novel drugs in the treatment of cancer. The current research work dealt with the synthesis of a series of 3-(3-acetyl-2-oxoquinolin-1-(2H)-yl-2-(substitutedphenyl)thiazolidin-4-one (Va-j) derivatives and evaluation of their in-vitro anticancer activity. All the synthesized compounds were satisfactorily characterized by IR and NMR data. Compounds were further evaluated for their in-vitro anticancer activity against A-549 (lung cancer) cell lines. The in-vitro anticancer activity was based upon the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) assay method. The synthesized compounds exhibited satisfactory anticancer properties against the A-549 cell line. The compound (VH): showed the highest potency amongst the tested derivatives against the A-549 cell line with IC50 values of 100 µg/ml respectively and was also found to be more potent than Imatinib (150 µg/ml) which was used as a standard drug. Molecular docking studies of the titled compounds (Va-j) were carried out using AutoDock Vina/PyRx software. The synthesized compounds exhibited well-conserved hydrogen bonds with one or more amino acid residues in the active pocket of the EGFRK tyrosine kinase domain (PDB 1m17). Among all the synthesized analogues, the binding affinity of the compound (Vh) was found to be higher than other synthesized derivatives and a molecular dynamics simulation study explored the stability of the docked complex system.

AMP(K)lifying NRF2 signalling: the influence of the AMPK activator metformin on Nrf2 and Bach1 levels as well as on phenotypic responses in A549 lung cancer cells

AMP(K)lifying NRF2 signalling: the influence of the AMPK activator metformin on Nrf2 and Bach1 levels as well as on phenotypic responses in A549 lung cancer cells

Assessment of the biological activity of Marrubium friwaldskyanum Boiss. (Lamiaceae)

Present scientific evidences about the biological activity and potential medical application of extracts derived from Marrubium friwaldskyanum Boiss. are limited. Therefore, our study was undertaken to define several main characteristics in this regard – in vitro cytotoxicity and antitumor properties, antibacterial activity and immunomodulatory potential. Extracts were obtained from different aerial parts of Marrubium friwaldskyanum – stems, leaves and flowers. The in vitro cytotoxicity and antitumor activity of the samples were evaluated by tetrazolium salt reduction tests and Neutral red uptake assays using four human cell lines (a normal fibroblastic and three adenocarcinoma cell lines/A549, HeLa, HT-29/) and by experiments with HT-29 tumor spheroids. Antibacterial activity toward Gram-negative (Escherichia coli) and Gram-positive (Bacillus cereus) species was assessed based on estimation of minimal inhibitory and minimal bactericidal concentrations as well as longitudinal studies on bacterial viability. Ex vivo assays with normal leukocytes were performed to define potential immunomodulatory activity of the extracts. Our results demonstrated selective antitumor activity of the extracts directed against colon adenocarcinoma HT-29 cells and cervical adenocarcinoma HeLa cell line. Metabolic activity of A549 lung adenocarcinoma cells was affected only by the sample derived from flowers. M. friwaldskyanum leaf and flower extracts showed the highest activity, which included reduction of HT-29 tumor spheroid growth and viability. The studied samples exhibited antibacterial activity against both bacterial species tested. Treatment with M. friwaldskyanum extracts affected specific leukocyte populations (HLA+, CD19+, CD11b+, CD25+ cells). These results demonstrate for the first time complex biological effects of extracts derived from M. friwaldskyanum and their potential to serve as a source of valuable compounds for the pharmaceutical industry.

Evaluation of DNA and BSA-Binding, Nuclease Activity, and Anticancer Properties of New Cu(II) and Ni(II) Complexes with Quinoline-Derived Sulfonamides

Four complexes of essential metal ions, Cu(II) and Ni(II), with the new sulfonamide ligand N-(pyridin-2-ylmethyl)quinoline-8-sulfonamide (HQSMP) were synthesized and physicochemically and structurally characterized. Complex [Cu(QSMP)Cl]n (2) consists of a polymeric chain formed by distorted square pyramidal units. In 2, the sulfonamide ligand acts as a bridge coordinating to one Cu(II) through its three N atoms and to another metal ion via one O atom in the sulfonamido group, while the pentacoordinate complex [Cu(QSMP)(C6H5COO)] (3) presents a highly distorted square pyramidal geometry. Complex [Ni(QSMP)(C6H5COO)(CH3OH)][Ni(QSMP)(CH3COO)(CH3OH)] (4) consists of two mononuclear entities containing different anion coligands, either a benzoate or an acetate group. Both units exhibit a distorted octahedral geometry. The interaction of the complexes with CT-DNA was studied by means of UV-Vis and fluorescence spectroscopy, interestingly revealing that the Ni(II) complex presents the highest affinity towards the nucleic acid. Complexes 1 and 2 are able to cleave DNA. Both compounds show promising nuclease activity at relatively low concentrations by mediating the production of a reactive oxygen species (ROS). The interaction of the four complexes with bovine serum albumin (BSA) was also investigated, showing that the compounds can bind to serum proteins. The antitumor potential of complexes 1 and 2 was evaluated against the A549 lung adenocarcinoma cell line, revealing cytotoxic properties that were both dose- and time-dependent.