Human Lung Cancer Cells Research Articles

Lonidamine Increases the Cytotoxic Effect of 1-[(4-Amino-2-methyl-5-pyrimidinyl)methyl]-3-(2-chloroethyl)-3-nitrosourea via Energy Inhibition, Disrupting Redox Homeostasis, and Downregulating MGMT Expression in Human Lung Cancer Cell Line.

Lung cancer ranks as the second most diagnosed cancer and the leading cause of cancer-related deaths worldwide. Novel chemotherapeutic strategies are crucial to efficiently target tumor cells while minimizing toxicity to normal cells. In this study, we proposed a combination strategy using energy blocker lonidamine (LND) and cytotoxic drug nimustine (ACNU, 1-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-3-(2-chloroethyl)-3-nitrosourea) to enhance the killing of a human lung cancer cell line and investigated the potential chemo-sensitizing mechanism of LND. LND was found to remarkably increase the cytotoxicity of ACNU to A549 and H1299 cells without significantly affecting normal lung BEAS2B cells. The combination of LND and ACNU also produced significant effects on cell apoptosis, colony formation, cell migration, and invasion assays compared to single drug treatment. Mechanistically, LND decreased intracellular ATP levels by inhibiting glycolysis and inducing mitochondrial dysfunction. Furthermore, the combination of LND and ACNU could intensify cellular oxidative stress, decrease cellular GSH contents, and increase reactive oxygen species (ROS) production. Notably, LND alone dramatically downregulated the expression of DNA repair protein MGMT (O6-methylguanine-DNA methyltransferase), enhancing DNA interstrand cross-link formation induced by ACNU. Overall, LND represents a potential chemo-sensitizer to enhance ACNU therapy through energy inhibition, disrupting redox homeostasis and downregulating MGMT expression in human lung cancer cell line under preclinical and clinical background.

Unveiling the synergistic potential of g-C3N4-MWCNT/In2O3 nanocomposite for enhanced organic pollutant degradation and cancer cell inhibition under visible light irradiation

The surge in industrial activities and a substantial increase in antibiotic usage, has led to the further deterioration of global water pollution problems. Focusing on this current scenario, we synthesize the g-C3N4-MWCNT/In2O3 (GMI) ternary composite to utilize for the photocatalytic degradation of levofloxacin (LF) antibiotic and crystal violet (CV) dye under visible light. The photocatalytic degradation of CV (15 mgL⁻1) and LF (40 mgL⁻1) was 99.7 % and 87.4 % respectively, in just 15 and 100 min of irradiation with GMI-0.2 nanocomposite. The removal rates of CV and LF with GMI-0.2 nanocomposite were 14.61 and 4.85 times more rapid than those observed with In2O3. Similarly, compared to g-C3N4, the removal rates for CV and LF were 7.34 and 3.98 times higher when using GMI-0.2 nanocomposite. The trapping experiments and ESR measurements indicated that O2•⁻ was the predominant active species responsible for the photocatalytic degradation processes. In order to explain the degradation processes, a feasible photocatalytic mechanism for GMI ternary composite was proposed. The mechanism was based on the calculations of the band gaps and edge potentials of the synthesised materials as well as the findings of the quenching experiments. The GMI-0.2 nanocomposite was also used to treat human lung cancer cells, and it was discovered that cell viability with 100 µg/mL of the photocatalyst was lowest in both dark (36 %) and in visible light (20 %).

Downregulation of Rad51 Expression and Activity Potentiates the Cytotoxic Effect of Osimertinib in Human Non-Small Cell Lung Cancer Cells.

Osimertinib (AZD9291) is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that has shown significant clinical benefits in patients with EGFR-sensitizing mutations or the EGFR T790M mutation. The homologous recombination (HR) pathway is crucial for repairing DNA double-strand breaks (DSBs). Rad51 plays a central role in HR, facilitating the search for homology and promoting DNA strand exchange between homologous DNA molecules. Rad51 is overexpressed in numerous types of cancer cells. B02, a specific small molecule inhibitor of Rad51, inhibits the DNA strand exchange activity of Rad51. Previous studies have indicated that B02 disrupted Rad51 foci formation in response to DNA damage and inhibited DSBs repair in human cells and sensitized them to chemotherapeutic drugs in vitro and in vivo. However, the potential therapeutic effects of combining osimertinib with a Rad51 inhibitor are not well understood. The aim of this study was to elucidate whether the downregulation of Rad51 expression and activity can enhance the osimertinib-induced cytotoxicity in non-small cell lung cancer (NSCLC) cells. We used the MTS, trypan blue dye exclusion and colony-formation ability assay to determine whether osimertinib alone or in combination with B02 had cytotoxic effects on NSCLC cell lines. Real-time polymerase chain reaction was conducted to measure the amounts of Rad51 mRNA. The protein levels of phosphorylated AKT and Rad51 were determined by Western blot analysis. We found that osimertinib reduced Rad51 expression by inactivating AKT activity. Rad51 knockdown using small interfering RNA or AKT inactivation through the phosphatidylinositol 3-kinase inhibitor LY294002 or si-AKT RNA transfection enhanced the cytotoxic and growth inhibitory effects of osimertinib. In contrast, AKT-CA (a constitutively active form of AKT) vector-enforced expression could mitigate the cytotoxic and cell growth inhibitory effects of osimertinib. Furthermore, B02 significantly enhanced the cytotoxic and cell growth inhibitory effects of osimertinib in NSCLC cells. Compared to parental cells, the activation of AKT and Rad51 expression in osimertinib-resistant cells could not be significantly inhibited by osimertinib treatment. Moreover, the increased expression of Rad51 is associated with the resistance mechanism in osimertinib-resistant H1975 and A549 cells. Collectively, the downregulation of Rad51 expression and activity enhances the cytotoxic effect of osimertinib in human NSCLC cells.

Kopsileuconines A−D: Bisindole alkaloids with cytotoxic activity from Kopsia hainanensis

Kopsileuconines A−D (1−4), four monoterpenoid bisindole alkaloids with unprecedented skeletons, along with their biosynthetically related precursors (5−8) were isolated from the roots of Kopsia hainanensis. Compound 1 possessed an undescribed C-6−C-5′ dimerization pattern of aspidofractinine-type alkaloids. Compounds 2−4 were rhazinilam-kopsine (2) and rhazinilam-aspidofractinine type (3 and 4) bisindole alkaloids with undescribed skeletons, respectively. Their structures with absolute configurations were fully accomplished by extensive spectroscopic analysis, quantum-chemical calculations, and X-ray crystallography. A plausible biosynthetic pathway for 1−4 was proposed. Compound 2 exhibited a significant inhibitory effect against human lung cancer cell lines PC9 (EGFR mutant), with an IC50 value of 15.07 ± 1.19 μM.

Polycyclic polyprenylated acylphloroglucinols from the pericarps of Garcinia multiflora champ. ex Benth. with cytotoxic property

The phytochemical investigation on the pericarps of Garcinia multiflora resulted in the isolation of 12 previously undescribed polycyclic polyprenylated acylphloroglucinols (PPAPs, 1–12) with a variety of skeletons. Their structures were determined by comprehensive spectroscopic analyses, ECD calculations, and single-crystal X-ray diffraction. Compounds 6–9 possess a rare bicyclo[4.3.1]decane skeleton. Additionally, the anti-tumor activity of the 12 isolates was evaluated. The results indicated that compounds 5, 9, and 12 exhibited significant cytotoxicity in a wide range of cancer cell lines, including the human breast cancer MDA-MB-231 cells, human lung cancer A549 cells, human colon cancer SW480 cells and human ovarian cancer HEY cells. Further studies indicated that compound 5 induced cell cycle arrest and apoptosis, to inhibit the growth of MDA-MB-231 cells. Taken together, these findings expand the chemical diversity of PPAPs and further demonstrate the potential of PPAPs as candidates for cancer treatment.

Anti-Growth and Anti-Metastatic Potential of Raw and Thermally Treated Eragrostis tef Extract in Human Cancer Cells.

Teff (Eragrostis tef), a gluten-free cereal crop cultivated originally in Northeast Africa, is increasingly utilized due to its nutritional and health benefits. The aim of the present study was to investigate the effects of ethanol extract obtained from raw and thermally treated teff, referred to as RTE and TTE, respectively, on uncontrolled growth and activated metastasis using human cancer cell lines. Both RTE and TTE contained flavones, such as orientin (luteolin 8-C-glucoside) and vitexin (apigenin 8-C-glucoside), and phenolic acids, such as protocatechuic acid and p-coumaric acid. TTE showed higher total phenol, protocatechuic acid, and p-coumaric acid contents, but lower orientin content compared to RTE. RTE and TTE significantly suppressed cell growth of H1299 human lung cancer cells, with TTE exhibiting more pronounced effects than RTE, while both extracts had only minimal effects on the growth of non-malignant human umbilical vein endothelial cells. The growth-inhibitory activities of RTE and TTE in H1299 cells were associated with apoptosis induction and cell cycle arrest at the G2/M phase. TTE produced an additional effect on inducing cell cycle arrest at the S phase in H1299 cells, potentially contributing to its stronger growth-inhibitory effects. Moreover, both RTE and TTE effectively inhibited key events in metastasis, such as invasion, migration, and adhesion, in H1299 cells under non-cytotoxic conditions, with TTE showing stronger effects. In HCT116 human colon cancer cells, a similar pattern of inhibition was demonstrated against the metastatic events, accompanied by reduced levels of matrix metalloproteinase-2 and -9. Our results indicate that teff extracts exhibit in vitro anti-growth and anti-metastatic activities, which are enhanced by thermal treatment of teff.

Biomass extract-mediated preparation of magnesium-doped nickel oxide nanoparticles and their in vitro bioactivities assessment

Biomass extract-mediated fabrication of metal oxide nanoparticles received significant attention in material research because it is eco-friendly, cost-effective, and easy to scalability. Here, the fabrication of Boerhavia diffusa leaf extract (BDE)-mediated magnesium-doped nickel oxide nanoparticles (Mg-doped-NiO-BDE) and their in vitro bioactivities are reported. Several characterization procedures are used to characterize the prepared NiO nanoparticles. Field emission scanning electron microscopy and transmission electron microscopy images exhibit that the Mg-doped-NiO-BDE are distorted spherical. The X-ray diffraction showed that the average crystallite sizes of the nanoparticles are around 51–55 nm. X-ray diffraction, X-ray photoelectron spectroscopy, and energy-dispersive X-ray spectroscopy analysis results confirm that the NiO is produced, and Mg-doping has occurred in the adopted reaction condition. The doped NiO NPs exhibit broad-spectrum antibacterial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), as well as antifungal action against Aspergillus niger (A. nigar). The antioxidant, anti-inflammatory, and anti-diabetic efficiencies of doped-NiO NPs (concentration = 400 μg/mL) are around 65 %, 89 %, and 87 %, respectively. The Mg-doped-NiO-BDE nanoparticles show around 75 % viability against the human lung cancer cell line (A459) with a concentration of up to 100 μg/mL, while the IC50 value is 185.6 μg/mL. The scratch test is executed with the mouse fibroblast cells (L929) in which doped-NiO NPs exhibit around 36 % wound-closing ability. The above results signify that the fabricated Mg-doped-NiO-BDE is a potent bioactive material that could be used for biomedical applications.

Therapeutic Senolysis of Axitinib-Induced Senescent Human Lung Cancer Cells.

Tyrosine kinase inhibitors (TKIs) inhibit receptor-mediated signals in cells. Axitinib is a TKI with high specificity for vascular endothelial growth factor receptors (VEGFRs). We determined whether axitinib could induce senescence in human cancer cells and be lysed by the senolytic drug ABT-263. Human lung and breast adenocarcinoma cell lines were used. These cells were cultured with axitinib or a multi-target TKI lenvatinib. The expression of β-galactosidase, VEGFRs, Ki-67, reactive oxygen species (ROS) of cancer cells, and their BrdU uptake were evaluated by flow cytometry. The mRNA expression of p21 and IL-8 was examined by quantitative PCR. The effects of TKIs on phosphorylation of Akt and Erk1/2, as downstream molecules of VEGFR signaling, were examined by immunoblot. The in vivo anti-cancer effect was examined using a xenograft mice model. Axitinib, but not lenvatinib, induced cellular senescence (increased cell size and enhanced expression of β-galactosidase) in all adenocarcinoma cell lines. Axitinib-induced senescence was unrelated to the expression of VEGFRs on cancer cells. ROS were involved in axitinib-induced senescence. Axitinib-induced senescent lung adenocarcinoma A549 cells were drastically lysed by ABT-263. In A549-xenografted mice, combination therapy with axitinib and ABT-263 significantly suppressed tumor growth with the induction of apoptotic cancer cells.

Esterified styrene-maleic acid copolymer modified silica as mixed-mode polymer-brush stationary phases for chromatographic separation

Styrene-maleic acid (SMA) copolymer has received much attention for its excellent solubilization characteristics. In this work, SMA copolymer brush-based chromatographic stationary phases were exploited and developed for the first time. First, SMA copolymer brush was in situ grown on the surface of spherical silica via living/controlled reversible addition-fragmentation chain transfer (RAFT) polymerization method. Subsequently, as a proof-of-concept demonstration, the copolymer was esterified by diethylene glycol mono-2-ethylhexyl ether (DGME) and 2-(2-ethylhexyloxy) ethanol (EHOE), respectively. The obtained Sil-SMA-DGME and Sil-SMA-EHOE copolymer-brush chromatographic stationary phases were characterized by transmission electron microscopy, Fourier transform infrared spectrometer, X-ray photoelectron spectroscopy, and thermogravimetric analysis, respectively. The chromatographic retention mechanism indicated that both the two packed columns exhibited hydrophilic/reverse mixed-mode retention modes. The maximum column efficiency was up to 71,000 N/m. The chromatographic separation performance evaluation indicated that the novel kind of stationary phases had excellent separation capabilities for hydrophilic, hydrophobic compounds and phospholipid standards. In addition, by combination with mass spectrometry identification, the Sil-SMA-DGME column was further exploited for separation and identification of phospholipids in human lung cancer cells. Totally, 9 classes including 186 phospholipid species were successfully identified. The results demonstrated the promising application prospects of the novel kind of SMA copolymer-brush chromatographic stationary phases.

Nano-Liposomal Beetroot Phyto-Pigment in Photodynamic Therapy as a Prospective Green Approach for Cancer Management: In Vitro Evaluation and Molecular Dynamic Simulation.

Using plant extracts as photosensitizers in photodynamic therapy (PDT) represents a significant green approach toward sustainability. This study investigates beetroot juice (BRJ), betanin, and their liposomal formulations (Lip-BRJ, Lip-Bet) as photosensitizers in cancer PDT. BRJ was prepared, and its betanin content was quantified via HPLC. The p-nitrosodimethylaniline (RNO)/imidazole technique monitored the singlet oxygen formation. BRJ and betanin decreased the RNO absorbance at 440 nm by 12% and 9% after 45 min of irradiation, respectively. Furthermore, betanin interaction with Bcl-2 proteins was examined using binding free energy analysis and molecular dynamic simulation. The results revealed favorable interactions with ΔG values of -40.94 kcal/mol. Then, BRJ, betanin, Lip-BRJ, and Lip-Bet were tested as photosensitizers on normal (HEK 293) and human lung cancer (A549) cell lines. Irradiation significantly enhanced the cytotoxicity of Lip-Bet on HEK 293 cells (20% cell viability at 2000 µg/mL) and A549 cells (13% cell viability at 1000 µg/mL). For Lip-BRJ, irradiation significantly enhanced the cytotoxicity on HEK 293 cells at lower concentrations and on A549 cells at all tested concentrations. These results proved the positive effect of light and liposomal encapsulation on the anticancer activity of betanin and BRJ, suggesting the efficiency of liposomal beetroot pigments as green photosensitizers.

꾸지뽕나무 열매 당침액 이용 콤부차의 이화학적 품질 특성 및 인체 폐암세포 항증식 활성

This study was conducted to develop kombucha with better functionality. The developed kombucha (CK) was prepared using the sugar extracts from fruits of Cudrania tricuspidata (Carrière) Bureau ex Lavallée instead of the sugar, which is used as a substrate for SCOBY in conventional kombucha (K). During fermentation, the soluble solids content significantly decreased in CK compared to K, and the pH change decreased rapidly in CK compared to K. On the 14th day of fermentation, the weight of the SCOBY in CK was higher than that in K. Immediately after preparation, K contained only sucrose, but CK contained sucrose, glucose, and fructose. SCOBY appears to use glucose and fructose preferentially during fermentation. K contained acetic acid and citric acid right after preparation. However, as fermentation progressed, the composition changed to acetic acid, citric acid, and lactic acid. At the same time, CK initially consisted of citric acid, lactic acid, and acetic acid. However, acetic acid and citric acid increased but lactic acid decreased significantly on the 14th day of fermentation. In the cytotoxicity studies, the CK showed a proliferation-promoting effect on normal lung cells (MRC-5) and strong cytotoxicity against human lung cancer cells (A549). These results suggest that the kombucha made from sugar extracts of C. tricuspidata fruits can be used as a more functional beverage than regular kombucha.

꾸지뽕나무 열매 당침액 이용 콤부차의 이화학적 품질 특성 및 인체 폐암세포 항증식 활성

This study was conducted to develop kombucha with better functionality. The developed kombucha (CK) was prepared using the sugar extracts from fruits of Cudrania tricuspidata (Carrière) Bureau ex Lavallée instead of the sugar, which is used as a substrate for SCOBY in conventional kombucha (K). During fermentation, the soluble solids content significantly decreased in CK compared to K, and the pH change decreased rapidly in CK compared to K. On the 14th day of fermentation, the weight of the SCOBY in CK was higher than that in K. Immediately after preparation, K contained only sucrose, but CK contained sucrose, glucose, and fructose. SCOBY appears to use glucose and fructose preferentially during fermentation. K contained acetic acid and citric acid right after preparation. However, as fermentation progressed, the composition changed to acetic acid, citric acid, and lactic acid. At the same time, CK initially consisted of citric acid, lactic acid, and acetic acid. However, acetic acid and citric acid increased but lactic acid decreased significantly on the 14th day of fermentation. In the cytotoxicity studies, the CK showed a proliferation-promoting effect on normal lung cells (MRC-5) and strong cytotoxicity against human lung cancer cells (A549). These results suggest that the kombucha made from sugar extracts of C. tricuspidata fruits can be used as a more functional beverage than regular kombucha.

Bazedoxifene Inhibits Cell Viability, Colony-Forming Activity, and Cell Migration in Human Non-Small Cell Lung Cancer Cells and Improves the Treatment Efficacy of Paclitaxel and Gemcitabine.

Bazedoxifene is a third-generation selective estrogen receptor modulator that inhibits the IL6/IL6R/GP130 signaling pathway by inhibiting IL6-induced homodimerization of GP130. Considering that the IL6/IL6R/GP130 signaling pathway is important in tumorigenesis and metastasis, bazedoxifene is thought to have an antitumor effect, which has been proven preliminarily in breast cancer and pancreatic cancer but has not yet been studied in non-small cell lung cancer (NSCLC). This study is aimed at evaluating the antitumor effect of bazedoxifene in NSCLC. A549 and H1299 NSCLC cell lines were employed and exposed to various concentrations of bazedoxifene, paclitaxel, gemcitabine, and their combinations for cell viability, colony formation, and wound healing assays to demonstrate the antitumor effect of bazedoxifene with or without paclitaxel or gemcitabine. MTT cell viability, colony formation, and wound healing assays showed that bazedoxifene was capable of inhibiting cell viability, colony formation, and cell migration in a dose-dependent manner. In addition, bazedoxifene was capable of working with paclitaxel or gemcitabine synergistically to inhibit cell viability, colony formation, and cell migration. This study demonstrated the potential antitumor effect of bazedoxifene and its ability to improve the treatment efficacy of paclitaxel and gemcitabine.

Increased Radioresistance of Human Non-Small Cell Lung Cancer Cells Surviving Cisplatin Exposure

Increased Radioresistance of Human Non-Small Cell Lung Cancer Cells Surviving Cisplatin Exposure

In vitro cytotoxic activity of chemically synthesized ZnTe nanoparticles against human lung cancer cell line L-132 with supported molecular docking study

Among all the cancer cases, Lung cancer is the most common worldwide, which needs more potential therapy. But there are many limitations in the present therapy used for lung cancer treatment. Recently, many researchers are using different types of nanoparticles as an alternative for this purpose. Here, with such interest, ZnTe nanocrystals have been synthesized using a wet-chemical method, which is a cost-effective and easy method. After preparing the ZnTe nanocrystals, morphology has been analyzed through a scanning electron microscope (SEM) and the crystallinity of the prepared ZnTe nanocrystals has been investigated using X-ray diffraction analysis. After that, cytotoxicity of the prepared ZnTe nanoparticles has been examined at three different concentrations (100 ng/ml, 1 μg/ml, 100 μg/ml) on human lung cancer cell line L-132 using the MTT assay. From the experimental results, it is observed that a batter percentage of about 56 % of killing has been obtained at the concentration of 100 μg/ml after 24 h of treatment. It may happen that ZnTe nanoparticles enter through the cell membrane and induce cell apoptosis. For better understanding, molecular docking has been performed using ‘auto dock vina’ to find the binding confirmation of ZnTe nanoparticles with the lung cancer cell line L-132. Both the biological and computational methods confirm that nanocrystalline ZnTe is a therapeutic candidate for the treatment of lung cancer cells.

Molecular Hybrid Design, Synthesis, In Vitro Cytotoxicity, In Silico ADME and Molecular Docking Studies of New Benzoate Ester-Linked Arylsulfonyl Hydrazones.

In this paper, we present the synthesis and characterization of two known sulfonyl hydrazides (1 and 2) and their new sulfonyl hydrazone derivatives (9-20), as well as in vitro and in silico investigations of their cytotoxic properties against human lung (A549) and human breast (MCF-7) cancer cell lines. The target compounds (9-20) obtained in high yields were synthesized for the first time by a multi-step reaction, and their structures were confirmed by elemental analysis and various spectral techniques, including FT-IR, 1H-, and 13C-NMR. The antiproliferative profiles of these compounds (1, 2, and 9-20) in this study were determined at concentrations of 200, 100, 50, and 25 µM against selected cancer cell lines for 72 h using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) method. Except for compounds 1 and 2, other compounds (9-20) demonstrated cytotoxic activity at concentrations lower than 200 µM. The newly synthesized compounds (9-20) demonstrated antiproliferative activities at a micromolar level, with IC50 values in the range of 29.59-176.70 μM for the A549 cell line and 27.70-170.30 μM for the MCF-7 cell line. Among these compounds, compound 15 (IC50 = 29.59 μM against A549 cell line and IC50 = 27.70 μM against MCF-7 cell line) showed the highest cytotoxic activity against these two cancer cell lines compared to the reference drug cisplatin (IC50 = 22.42 μM against A549 cell line and IC50 = 18.01 μM against MCF-7 cell line). From docking simulations, to establish a plausible binding mode of compounds, we noticed that compound 15 demonstrated the highest affinity (-6.8508 kcal/mol) for estrogen receptor-beta (ERbeta) compared to others, suggesting promising ERbeta binding potential. Most compounds followed Lipinski's rule of five, with acceptable logP values. Additionally, all had mixed gastrointestinal absorption and limited blood-brain barrier permeability. Overall, our study proposed new sulfonyl hydrazones as a potential class of anticancer agents.

COX-2/PTGS2-targeted herbal-derived oligonucleotide drug HQi-sRNA-2 was effective in spontaneous mouse lung cancer model.

In 2020, the number of deaths caused by lung cancer worldwide reached 1,796,144, making it the leading cause of cancer-related deaths. Cyclooxygenase-2/prostaglandin endoperoxide synthase 2 (COX-2/PTGS2) is overexpressed in lung cancer, which promotes tumor proliferation, invasion, angiogenesis, and resistance to apoptosis. Here, we report that the oligonucleotide drug HQi-sRNA-2 from Traditional Chinese Medicine Huangqin targeting COX-2/PTGS2 significantly inhibited proliferation, migration, and invasion and induced apoptosis in the human lung cancer cell line NCI-H460. Oral delivery of HQi-sRNA-2 bencaosomes prolonged survival, reduced tumor burden, and maintained weight in a spontaneous mouse lung cancer model. Compared with paclitaxel, HQi-sRNA-2 may be less toxic and have approximately equal efficacy in reducing tumor burden. Our previous studies reported that herbal small RNAs (sRNAs) are functional medical components. Our data suggest that sphingosine (d18:1)-HQi-sRNA-2 bencaosomes, targeting COX-2/PTGS2 and downregulating the PI3K and AKT signaling pathways, may provide novel therapeutics for lung cancer.

Prognostic and Potential Therapeutic Roles of PRKDC Expression in Lung Cancer.

PRKDC is a key factor involved in the ligation step of the non-homologous end joining pathway. Its dysfunction has proven to be a biomarker for radiosensitivity of cancer cells. However, the prognostic value of PRKDC and its underlying mechanisms have not been clarified yet. In this study, we found that PRKDC overexpressed in lung adenocarcinoma (LUAD) and is significantly related to unfavorable survival, while downregulation of PRKDC is link to inflamed tumor immune signature. Our further in vitro results also showed a potent antitumor efficacy of PRKDC inhibitors alone or combined with cisplatin in human lung cancer cells. This study demonstrated that PRKDC is a potential prognostic biomarker, immunotherapy target, and promising combination candidate for chemotherapy for lung cancer, and highlighted the potential of PRKDC-targeted inhibitors for the treatment of lung cancer.

Studies on the thermal sensitivity of lung cancer cells exposed to an alternating magnetic field and magnesium-doped maghemite nanoparticles

BackgroundMagnetic fluid hyperthermia (MFH) represents a promising therapeutic strategy in cancer utilizing the heating capabilities of magnetic nanoparticles when exposed to an alternating magnetic field (AMF). Because the efficacy and safety of MFH treatments depends on numerous intrinsic and extrinsic factors, therefore, the proper MFH setups should focus on thermal energy dosed into the cancer cells.MethodsIn this study, we performed MFH experiments using human lung cancer A549 cells (in vitro) and NUDE Balb/c mice bearing human lung (A549) cancer (in vivo). In these two experimental models, the heat was induced by magnesium-doped iron(III) oxide nanoparticles coated with mPEG-silane (Mg0.1-γ-Fe2O3(mPEG-silane)0.5) when exposed to an AMF.ResultsWe observed that the lung cancer cells treated with Mg0.1-γ-Fe2O3(mPEG-silane)0.5 (0.25 mg·mL−1) and magnetized for 30 min at 14.4 kA·m−1 yielded a satisfactory outcome in reducing the cell viability up to ca. 21% (in vitro). The activation energy calculated for this field strength was estimated for 349 kJ·mol−1. Both volumetric measurements and tumor mass assessments confirmed by magnetic resonance imaging (MRI) showed a superior thermal effect in mice bearing human lung cancer injected intratumorally with Mg0.1-γ-Fe2O3(mPEG-silane)0.5 nanoparticles (3 mg·mL−1) and subjected to an AMF (18.3 kA·m−1) for 30 min four times at weekly intervals. Research demonstrated that mice undergoing MFH exhibited a marked suppression of tumor growth (V = 169 ± 94 mm3; p < 0.05) in comparison to the control group of untreated mice. The CEM43 (cumulative number of equivalent minutes at 43 °C) value for these treatments were estimated for ca. 9.6 min with the specific absorption rate (SAR) level ranging from 100 to 150 W·g−1.ConclusionsThe as-obtained results, both cytotoxic and those related to energy calculations and SAR, may contribute to the advancement of thermal therapies, concurrently indicating that the proposed magnetic fluid hyperthermia holds a great potential for further testing in the context of medical applications.Graphical

Targeting hyaluronan metabolism-related molecules associated with resistant tumor-initiating cells potentiates chemotherapy efficacy in lung cancer

The success of chemotherapy regimens in patients with non-small cell lung cancer (NSCLC) could be restricted at least in part by cancer stem cells (CSC) niches within the tumor microenvironment (TME). CSC express CD133, CD44, CD47, and SOX2, among other markers and factors. Analysis of public data revealed that high expression of hyaluronan (HA), the main glycosaminoglycan of TME, correlated positively with CSC phenotype and decreased disease-free interval in NSCLC patients. We aimed to cross-validate these findings on human and murine lung cancer cells and observed that CD133 + CSC differentially expressed higher levels of HA, HAS3, ABCC5, SOX2, and CD47 (p < 0.01). We modulated HA expression with 4-methylumbelliferone (4Mu) and detected an increase in sensitivity to paclitaxel (Pa). We evaluated the effect of 4Mu + chemotherapy on survival, HA metabolism, and CSC profile. The combination of 4Mu with Pa reduced the clonogenic and tumor-forming ability of CSC. Pa-induced HAS3, ABCC5, SOX2, and CD47 expression was mitigated by 4Mu. Pa + 4Mu combination significantly reduced in vivo tumor growth, enhancing animal survival and restoring the CSC profile in the TME to basal levels. Our results suggest that HA is involved in lung CSC phenotype and chemosensitivity, and its modulation by 4Mu improves treatment efficacy to inhibit tumor progression.