Nano-encapsulated chlorophyllin significantly delays progression of lung cancer both in in vitro and in vivo models through activation of mitochondrial signaling cascades and drug-DNA interaction

2016 ◽  
Vol 46 ◽  
pp. 147-157 ◽  
Author(s):  
Jayeeta Das ◽  
Asmita Samadder ◽  
Jesmin Mondal ◽  
Suresh K. Abraham ◽  
Anisur Rahman Khuda-Bukhsh
Keyword(s):  
Lung Cancer ◽  
Dna Interaction ◽  
Signaling Cascades ◽  
In Vivo Models ◽  
Mitochondrial Signaling

scholarly journals Hyaluronate Functionalized Multi-Wall Carbon Nanotubes Filled with Carboplatin as a Novel Drug Nanocarrier against Murine Lung Cancer Cells

Nanomaterials ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. 1572 ◽  
Author(s):  
Daniel Salas-Treviño ◽  
Odila Saucedo-Cárdenas ◽  
María de Jesús Loera-Arias ◽  
Humberto Rodríguez-Rocha ◽  
Aracely García-García ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Carbon Nanotubes ◽  
Tumor Cells ◽  
Therapeutic Potential ◽  
Cell Uptake ◽  
In Vivo Models ◽  
Multi Wall Carbon Nanotubes ◽  
Lung Cancer Model

Carbon nanotubes (CNTs) have emerged in recent years as a potential option for drug delivery, due to their high functionalization capacity. Biocompatibility and selectivity using tissue-specific biomolecules can optimize the specificity, pharmacokinetics and stability of the drug. In this study, we design, develop and characterize a drug nanovector (oxCNTs-HA-CPT) conjugating oxidated multi-wall carbon nanotubes (oxCNTs) with hyaluronate (HA) and carboplatin (CPT) as a treatment in a lung cancer model in vitro. Subsequently, we exposed TC–1 and NIH/3T3 cell lines to the nanovectors and measured cell uptake, cell viability, and oxidative stress induction. The characterization of oxCNTs-HA-CPT reveals that on their surface, they have HA. On the other hand, oxCNTs-HA-CPT were endocytosed in greater proportion by tumor cells than by fibroblasts, and likewise, the cytotoxic effect was significantly higher in tumor cells. These results show the therapeutic potential that nanovectors possess; however, future studies should be carried out to determine the death pathways involved, as well as their effect on in vivo models.

scholarly journals Ganetespib (STA-9090), a Nongeldanamycin HSP90 Inhibitor, Has Potent Antitumor Activity in In Vitro and In Vivo Models of Non–Small Cell Lung Cancer

2012 ◽  
Vol 18 (18) ◽  
pp. 4973-4985 ◽  
Author(s):  
Takeshi Shimamura ◽  
Samanthi A. Perera ◽  
Kevin P. Foley ◽  
Jim Sang ◽  
Scott J. Rodig ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Antitumor Activity ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Hsp90 Inhibitor ◽  
Small Cell ◽  
Small Cell Lung ◽  
In Vivo Models

Elevated circASCC3 Suppresses Antitumor Immunity by Sponging miR-432-5p to Upregulate C5a in Non-small-cell Lung Cancer

2021 ◽  
Author(s):  
Jian Gao ◽  
Ling-Xian Zhang ◽  
Yong-Qiang Ao ◽  
Chun Jin ◽  
Peng-Fei Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Malignant Phenotype ◽  
In Vivo Models ◽  
Normal Tissues

Abstract Background: Tumor invasion and immune evasion are the main mechanisms underlying the progression of non-small-cell lung cancer (NSCLC). In addition, abnormally expressed circular RNAs (circRNAs) contribute to the malignant phenotype of NSCLC. Thus, further investigation of the mechanism of dysregulated circRNAs may provide new insight into the treatment of NSCLC.Methods: circRNA sequencing was used to explore the different expression profiles of circRNAs in 4 NSCLC tissues and paired normal tissues. Then, the expression of key circRNAs in NSCLC tissues and matched normal tissues was further evaluated via in situ hybridization and in cell lines using quantitative real-time polymerase chain reaction (qRT-PCR). Next, in vitro and in vivo models of NSCLC were employed to uncover the functions and mechanisms of key circRNAs in NSCLC progression and treatment.Results: circASCC3 (hsa_circ_0077495) was overexpressed in NSCLC tissues compared to paired normal tissues, and the upregulation of circASCC3 indicated a dismal prognosis in patients with NSCLC. Overexpressed circASCC3 enhanced the malignant phenotype of NSCLC cells in vitro and led to an immunosuppressive microenvironment in vivo. Mechanistically, circASCC3 sponged miR-432-5p to increase the expression of complement C5a, which induced the progression and dysfunctional immune status of NSCLC. Moreover, the combination of the C5aR inhibitor PMX-53 and anti-programmed cell death 1 (PD-1) antibody achieved synergistic effects in NSCLC models overexpressing circASCC3.Conclusion: These results uncover the contributions of circASCC3 to NSCLC progression and immunosuppression and provide a potential strategy for overcoming resistance to anti-PD-1 therapy.

scholarly journals Effect of Oversulfation on the Composition, Structure, and In Vitro Anti-Lung Cancer Activity of Fucoidans Extracted from Sargassum aquifolium

Marine Drugs ◽  
2021 ◽  
Vol 19 (4) ◽  
pp. 215
Author(s):  
Hui-Hua Hsiao ◽  
Tien-Chiu Wu ◽  
Yung-Hsiang Tsai ◽  
Chia-Hung Kuo ◽  
Ren-Han Huang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Biological Activities ◽  
Annexin V ◽  
Structural Features ◽  
Signaling Cascades ◽  
Cytochrome C Release ◽  
Wide Range ◽  
Cancer Activity

Intensive efforts have been undertaken in the fields of prevention, diagnosis, and therapy of lung cancer. Fucoidans exhibit a wide range of biological activities, which are dependent on the degree of sulfation, sulfation pattern, glycosidic branches, and molecular weight of fucoidan. The determination of oversulfation of fucoidan and its effect on anti-lung cancer activity and related signaling cascades is challenging. In this investigation, we used a previously developed fucoidan (SCA), which served as a native fucoidan, to generate two oversulfated fucoidan derivatives (SCA-S1 and SCA-S2). SCA, SCA-S1, and SCA-S2 showed differences in compositions and had the characteristic structural features of fucoidan by Fourier transform infrared (FTIR) and nuclear magnetic resonance (NMR) analyses. The anticancer properties of SCA, SCA-S1, and SCA-S2 against human lung carcinoma A-549 cells were analyzed in terms of cytotoxicity, cell cycle, Bcl-2 expression, mitochondrial membrane potential (MMP), expression of caspase-3, cytochrome c release, Annexin V/propidium iodide (PI) staining, DNA fragmentation, and the underlying signaling cascades. Our findings indicate that the oversulfation of fucoidan promotes apoptosis of lung cancer cells and the mechanism may involve the Akt/mTOR/S6 pathway. Further in vivo research is needed to establish the precise mechanism whereby oversulfated fucoidan mitigates the progression of lung cancer.

scholarly journals Circulating extracellular vesicles from individuals at high-risk of lung cancer induce pro-tumorigenic conversion of stromal cells through transfer of miR-126 and miR-320

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Francesca Pontis ◽  
Luca Roz ◽  
Mavis Mensah ◽  
Miriam Segale ◽  
Massimo Moro ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Endothelial Cells ◽  
High Risk ◽  
Cancer Patients ◽  
Extracellular Vesicles ◽  
In Vivo Models ◽  
Lung Cancer Patients

Abstract Background Extracellular vesicles (EVs) containing specific subsets of functional biomolecules are released by all cell types and analysis of circulating EVs can provide diagnostic and prognostic information. To date, little is known regarding the role of EVs both as biomarkers and potential key players in human lung cancer. Methods Plasma EVs were isolated from 40 cancer-free heavy-smokers classified according to a validated 24-microRNA signature classifier (MSC) at high (MSCpos-EVs) or low (MSCneg-EVs) risk to develop lung cancer. EVs origin and functional properties were investigated using in vitro 3D cultures and in vivo models. The prognostic value of miRNAs inside EVs was assessed in training and in validation cohorts of 54 and 48 lung cancer patients, respectively. Results Different membrane composition, biological cargo and pro-tumorigenic activity were observed in MSCpos vs MSCneg-EVs. Mechanistically, in vitro and in vivo results showed that miR-126 and miR-320 from MSCpos-EVs increased pro-angiogenic phenotype of endothelial cells and M2 polarization of macrophage, respectively. MSCpos-EVs prompted 3D proliferation of non-tumorigenic epithelial cells through c-Myc transfer. Moreover, hypoxia was shown to stimulate the secretion of EVs containing c-Myc from fibroblasts, miR-126-EVs from endothelial cells and miR-320-EVs from granulocytes. Lung cancer patients with higher levels of mir-320 into EVs displayed a significantly shorter overall survival in training [HR2.96] and validation sets [HR2.68]. Conclusion Overall our data provide a new perspective on the pro-tumorigenic role of circulating EVs in high risk smokers and highlight the significance of miR-320-EVs as a new prognostic biomarker in lung cancer patients.

scholarly journals From Biology to Therapy: Improvements of Therapeutic Options in Lung Cancer

2019 ◽  
Vol 18 (9) ◽  
pp. 1235-1240 ◽  
Author(s):  
Luigi Formisano ◽  
Valerie M. Jansen ◽  
Roberta Marciano ◽  
Roberto Bianco
Keyword(s):  
Lung Cancer ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Initial Response ◽  
Chemotherapeutic Agents ◽  
Cancer Therapies ◽  
In Vivo Models ◽  
Egfr Tyrosine Kinase Inhibitors

Lung cancer is the leading cause of cancer-related mortality around the world, despite effective chemotherapeutic agents, the prognosis has remained poor for a long time. The discovery of molecular changes that drive lung cancer has led to a dramatic shift in the therapeutic landscape of this disease. In “in vitro” and “in vivo” models of NSCLC (Non-Small Cell Lung Cancer), angiogenesis blockade has demonstrated an excellent anti-tumor activity, thus, a number of anti-angiogenic drugs have been approved by regulatory authorities for use in clinical practice. Much more interesting is the discovery of EGFR (Epithelial Growth Factor Receptor) mutations that predict sensitivity to the anti-EGFR Tyrosine Kinase Inhibitors (TKIs), a class of drugs that has shown to significantly improve survival when compared with standard chemotherapy in the first-line treatment of metastatic NSCLC. Nevertheless, after an initial response, resistance often occurs and prognosis becomes dismal. Biomolecular studies on cell line models have led to the discovery of mutations (e.g., T790M) that confer resistance to anti-EGFR inhibitors. Fortunately, drugs that are able to circumvent this mechanism of resistance have been developed and have been recently approved for clinical use. The discovery of robust intratumor lymphocyte infiltration in NSCLC has paved the way to several strategies able to restore the immune response. Thus, agents interfering with PD-1/PD-L1 (Programmed Death) pathways make up a significant portion of the armamentarium of cancer therapies for NSCLC. In all the above-mentioned situations, the basis of the success in treating NSCLC has started from understanding of the mutational landscape of the tumor.

scholarly journals Structural and functional analysis of lorlatinib analogs reveals roadmap for targeting diverse compound resistance mutations in ALK-positive lung cancer

2021 ◽  
Author(s):  
Aya Shiba-Ishii ◽  
Ted W Johnson ◽  
Ibiayi Dagogo-Jack ◽  
Mari Mino-Kenudson ◽  
Theodore R Johnson ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tyrosine Kinase ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Precision Oncology ◽  
Resistance Mutations ◽  
In Vivo Models ◽  
Alk Positive

The treatment approach to advanced, ALK-positive non-small cell lung cancer (NSCLC) utilizing sequential ALK tyrosine kinase inhibitors (TKIs) represents a paradigm of precision oncology. Lorlatinib is currently the most advanced, potent and selective ALK tyrosine kinase inhibitor (TKI) in the clinic. However, tumors invariably acquire resistance to lorlatinib, and after sequential ALK TKIs culminating with lorlatinib, diverse refractory compound ALK mutations can emerge. Here, we determine the spectrum of lorlatinib-resistant compound ALK mutations identified in patients after treatment with lorlatinib, the majority of which involve ALK G1202R or I1171N/S/T. By assessing a panel of lorlatinib analogs against compound ALK mutant in vitro and in vivo models, we identify structurally diverse lorlatinib analogs that harbor differential selective profiles against G1202R- versus I1171N/S/T-based compound ALK mutations. Structural analysis revealed that increased potency against compound mutations was achieved primarily through two different mechanisms of improved targeting of either G1202R- or I1171N/S/T-mutant kinases. Based on these results, we propose a classification of heterogenous ALK compound mutations designed to focus the development of distinct therapeutic strategies for precision targeting of compound resistance mutations following sequential TKIs.

Indirubin-3-monoxime and thymoquinone exhibit synergistic efficacy as therapeutic combination in in-vitro and in-vivo models of Lung cancer

2020 ◽  
Vol 43 (6) ◽  
pp. 655-665
Author(s):  
Ayed A. Dera ◽  
Prasanna Rajagopalan ◽  
Majed Al Fayi ◽  
Irfan Ahmed ◽  
Harish C. Chandramoorthy
Keyword(s):  
Lung Cancer ◽  
In Vivo Models

scholarly journals Lipidomics reveals that sustained SREBP-1-dependent lipogenesis is a key mediator of gefitinib-acquired resistance in EGFR-mutant lung cancer

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Chuncao Xu ◽  
Lei Zhang ◽  
Daifei Wang ◽  
Shiqin Jiang ◽  
Di Cao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
De Novo ◽  
Acquired Resistance ◽  
De Novo Lipogenesis ◽  
Egfr Mutations ◽  
In Vivo Models ◽  
Gefitinib Treatment ◽  
Egfr Mutant

AbstractPatients with EGFR mutations in non-small cell lung cancer (NSCLC) have been greatly benefited from gefitinib, however, the therapeutic has failed due to the presence of acquired resistance. In this study, we show that gefitinib significantly induces downregulation of Sterol Regulator Element Binding (SREBP1) in therapy-sensitive cells. However, this was not observed in EGFR mutant NSCLC cells with acquired resistance. Lipidomics analysis showed that gefitinib could differently change the proportion of saturated phospholipids and unsaturated phospholipids in gefitinib-sensitive and acquired-resistant cells. Besides, levels of ROS and MDA were increased upon SREBP1 inhibition and even more upon gefitinib treatment. Importantly, inhibition of SREBP1 sensitizes EGFR-mutant therapy-resistant NSCLC to gefitinib both in vitro and in vivo models. These data suggest that sustained de novo lipogenesis through the maintenance of active SRBEP-1 is a key feature of acquired resistance to gefitinib in EGFR mutant lung cancer. Taken together, targeting SREBP1-induced lipogenesis is a promising approach to overcome acquired resistance to gefitinib in EGFR-mutant lung cancer.

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