scholarly journals Therapeutic Potential of Zinc Oxide-Loaded Syringic Acid Against in vitro and in vivo Model of Lung Cancer

2020 ◽  
Vol Volume 15 ◽  
pp. 8249-8260
Author(s):  
Ning Yang ◽  
Feng Qiu ◽  
Feng Zhu ◽  
Lei Qi
Keyword(s):  
Lung Cancer ◽  
Zinc Oxide ◽  
Therapeutic Potential ◽  
Syringic Acid ◽  
In Vivo Model

scholarly journals Metabolic breakdown of non-small cell lung cancers by mitochondrial HSPD1 targeting

2021 ◽  
Author(s):  
Beatrice Parma ◽  
Vignesh Ramesh ◽  
Paradesi Naidu Gollavilli ◽  
Aarif Siddiqui ◽  
Luisa Pinna ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Progression ◽  
Therapeutic Potential ◽  
Small Cell ◽  
Small Cell Lung ◽  
Lung Cancers ◽  
Metabolism Enzymes ◽  
Shock Proteins

ABSTRACTThe identification of novel targets is of paramount importance to develop more effective drugs and improve the treatment of non-small cell lung cancer (NSCLC), the leading cause of cancer-related deaths worldwide. Since cells alter their metabolic rewiring during tumorigenesis and along cancer progression, targeting key metabolic players and metabolism-associated proteins represents a valuable approach with a high therapeutic potential. Metabolic fitness relies on the functionality of heat shock proteins (HSPs), molecular chaperones that facilitate the correct folding of metabolism enzymes and their assembly in macromolecular structures. Here, we show HSPD1 (HSP60) as a survival gene ubiquitously expressed in NSCLC and associated with poor patients’ prognosis. HSPD1 knockdown or its chemical disruption by the small molecule KHS101 induces a drastic breakdown of oxidative phosphorylation, and suppresses cell proliferation both in vitro and in vivo. By combining drug profiling with transcriptomics and through a whole-genome CRISPR/Cas9 screen, we demonstrate that HSPD1-targeted anti-cancer effects are dependent on OXPHOS and validated molecular determinants of KHS101 sensitivity, in particular, the creatine-transporter SLC6A8 and the subunit of the cytochrome c oxidase complex COX5B. These results highlight mitochondrial metabolism as an attractive target and HSPD1 as a potential theranostic marker for developing therapies to combat NCSLC.SignificanceHSPD1 elimination or disruption interferes with NSCLC metabolic activity causing a strong OXPHOS-dependent energetic breakdown, which the cancer cells fail to overcome, highlighting HSPD1 as a potential theranostic marker for improving lung cancer therapy.

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 Lactobacillus acidophilus attenuates downregulation of DRA function and expression in inflammatory models

2014 ◽  
Vol 307 (6) ◽  
pp. G623-G631 ◽  
Author(s):  
Varsha Singh ◽  
Anoop Kumar ◽  
Geetu Raheja ◽  
Arivarasu N. Anbazhagan ◽  
Shubha Priyamvada ◽  
...  
Keyword(s):  
Lactobacillus Acidophilus ◽  
Therapeutic Potential ◽  
Experimental Models ◽  
In Vivo Model ◽  
Inhibitory Effects ◽  
Inflammatory Models ◽  
Ifn Γ ◽  
Exchange Activity

Probiotics, including Lactobacilli, are commensal bacteria that have been used in clinical trials and experimental models for the prevention and treatment of diarrheal disorders. Our previous studies have shown that Lactobacillus acidophilus (LA) and its culture supernatant (CS) stimulated Cl−/HCO3− exchange activity, acutely via an increase in the surface levels of downregulated in adenoma (DRA, SLC26A3) and in long-term treatments via increasing its expression involving transcriptional mechanisms. However, the role of LA in modulating DRA activity under inflammatory conditions is not known. Current in vitro studies using human intestinal epithelial Caco-2 cells examined the efficacy of LA or its CS in counteracting the inhibitory effects of interferon-γ (IFN-γ) on Cl−/HCO3− exchange activity. Pretreatment of cells with LA or LA-CS for 1 h followed by coincubation with IFN-γ significantly alleviated the inhibitory effects of IFN-γ on Cl−/HCO3− exchange activity. In the in vivo model of dextran sulfate sodium-induced experimental colitis (3% in drinking water for 7 days) in C57BL/6J mice, administration of live LA (3 × 109 colony-forming units) via oral gavage attenuated colonic inflammation. LA administration also counteracted the colitis-induced decrease in DRA mRNA and protein levels. Efficacy of LA or its secreted soluble factors in alleviating inflammation and inflammation-associated dysregulation of DRA activity could justify their therapeutic potential in inflammatory diarrheal diseases.

In Vitro and in Vivo Studies of Poly-L-Lysine as Inducer of Friend Leukemic Cells Differentiation

1987 ◽  
Vol 73 (5) ◽  
pp. 431-436
Author(s):  
Rosanna Supino ◽  
Nadia Gibelli ◽  
Rosanna Nano ◽  
Gabriella Pezzoni ◽  
Franco Zunino
Keyword(s):  
Bone Marrow Cells ◽  
Therapeutic Potential ◽  
Leukemic Cells ◽  
In Vivo Studies ◽  
In Vivo Model ◽  
Treatment Schedule ◽  
Potent Inducer ◽  
Multiple Treatment

Poly-L-lysine, a synthetic cationic polypeptide known for its ability to bind to cell membranes, was found to induce differentiation of Friend leukemia cells « in vitro ». Studies were extended to the same « in vivo » model, in order to examine the therapeutic potential of this new differentiating agent. The i.p. administration of the polymer (Mw 2700) at the maximal tolerated dose resulted in major alterations of disease-related parameters. In particular, a multiple treatment schedule on the advanced disease resulted in a successful reduction of target organ weight and peripheral white blood cell count and appreciable differentiation of spleen and bone marrow cells. Apparently, the effects of poly-L-lysine were superior to those produced by N-methyl-acetamide, a potent inducer of differentiation « in vitro ».

scholarly journals Safety, Stability, and Therapeutic Efficacy of Long-Circulating TQ-Incorporated Liposomes: Implication in the Treatment of Lung Cancer

Pharmaceutics ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 153
Author(s):  
Arif Khan ◽  
Mohammed A. Alsahli ◽  
Mohammad A. Aljasir ◽  
Hamzah Maswadeh ◽  
Mugahid A. Mobark ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Binding Energy ◽  
Drug Targets ◽  
Therapeutic Potential ◽  
Nigella Sativa ◽  
Fold Increase ◽  
Dependent Manner ◽  
Bioactive Constituents

Thymoquinone (TQ), which is one of the main bioactive constituents of Nigella sativa seeds, has demonstrated its potential against various cancer models. The poor solubility of TQ in aqueous solution limits its uses in clinical application. The present study aimed to develop a novel formulation of TQ to increase its bioavailability and therapeutic potential with minimal toxicity. Polyethylene glycol (PEG)-coated DSPC/cholesterol comprising TQ liposomes (PEG-Lip-TQ) were prepared and characterized on various aspects. A computational investigation using molecular docking was used to assess the possible binding interactions of TQ with 12 prospective anticancer drug targets. The in vitro anticancer activity was assessed in A549 and H460 lung cancer cells in a time- and dose-dependent manner, while the oral acute toxicity assay was evaluated in silico as well as in vivo in mice. TQ docked to the Hsp90 target had the lowest binding energy of −6.05 kcal/mol, whereas caspase 3 was recognized as the least likely target for TQ with a binding energy of −1.19 kcal/mol. The results showed 96% EE with 120 nm size, and −10.85 mv, ζ-potential of PEG-Lip-TQ, respectively. The cell cytotoxicity data demonstrated high sensitivity of PEG-Lip-TQ and a several fold decrease in the IC50 while comparing free TQ. The cell cycle analysis showed changes in the distribution of cells with doses. The in vivo data revealed an ~9-fold increase in the LD50 of PEG-Lip-TQ on free TQ as an estimated 775 and 89.5 mg/kg b.w, respectively. This study indicates that the pharmacological and efficacy profile of PEG-lip-TQ is superior to free TQ, which will pave the way for an exploration of the effect of TQ formulation in the treatment of lung cancer in clinical settings.

scholarly journals Targeting the PI3K/AKT/mTOR Signaling Pathway in Lung Cancer: An Update Regarding Potential Drugs and Natural Products

Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 4100
Author(s):  
Iksen ◽  
Sutthaorn Pothongsrisit ◽  
Varisa Pongrakhananon
Keyword(s):  
Lung Cancer ◽  
Clinical Trials ◽  
Signaling Pathway ◽  
Therapeutic Potential ◽  
Mammalian Target Of Rapamycin ◽  
Tumor Development ◽  
Mtor Inhibitors ◽  
Mtor Signaling

Lung cancer is one of the most common cancers and has a high mortality rate. Due to its high incidence, the clinical management of the disease remains a major challenge. Several reports have documented a relationship between the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway and lung cancer. The recognition of this pathway as a notable therapeutic target in lung cancer is mainly due to its central involvement in the initiation and progression of the disease. Interest in using natural and synthetic medications to target these signaling pathways has increased in recent years, with promising results in vitro, in vivo, and in clinical trials. In this review, we focus on the current understanding of PI3K/AKT/mTOR signaling in tumor development. In addition to the signaling pathway, we highlighted the therapeutic potential of recently developed PI3K/AKT/mTOR inhibitors based on preclinical and clinical trials.

scholarly journals Ferroptosis in Non-Small Cell Lung Cancer: Progression and Therapeutic Potential on It

2021 ◽  
Vol 22 (24) ◽  
pp. 13335
Author(s):  
Jiayu Zou ◽  
Li Wang ◽  
Hailin Tang ◽  
Xiuxiu Liu ◽  
Fu Peng ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Progression ◽  
Cell Lung Cancer ◽  
Therapeutic Potential ◽  
Therapy Resistance ◽  
Small Cell ◽  
Small Cell Lung

As a main subtype of lung cancer, the current situation of non-small cell lung cancer (NSCLC) remains severe worldwide with a 19% survival rate at 5 years. As the conventional therapy approaches, such as chemotherapy, radiotherapy, targeted therapy, and immunotherapy, gradually develop into therapy resistance, searching for a novel therapeutic strategy for NSCLC is urgent. Ferroptosis, an iron-dependent programmed necrosis, has now been widely considered as a key factor affecting the tumorigenesis and progression in various cancers. Focusing on its effect in NSCLC, in different situations, ferroptosis can be triggered or restrained. When ferroptosis was induced in NSCLC, it was available to inhibit the tumor progression both in vitro and in vivo. The dominating mechanism was due to a regulation of the classic ferroptosis-repressed GSH-dependent GPX4 signaling pathway instead of other fractional regulating signal axes that regulated ferroptosis via impacting on the ROS, cellular iron levels, etc. In terms of the prevention of ferroptosis in NSCLC, an GSH-independent mechanism was also discovered, interestingly exhibiting the same upstream as the GPX4 signaling. In addition, this review summarizes the progression of ferroptosis in NSCLC and elaborates their association and specific mechanisms through bioinformatics analysis with multiple experimental evidence from different cascades. Finally, this review also points out the possibility of ferroptosis working as a novel strategy for therapy resistance in NSCLC, emphasizing its therapeutic potential.

scholarly journals Enhancement of Endometrial Receptivity by Cnidium officinale through Expressing LIF and Integrins

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Tae-Wook Chung ◽  
Mi-Ju Park ◽  
Hoyoung Lee ◽  
Keuk-Jun Kim ◽  
Cheorl-Ho Kim ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Embryo Implantation ◽  
Implantation Rate ◽  
Endometrial Receptivity ◽  
Female Infertility ◽  
In Vivo Model ◽  
Cnidium Officinale ◽  
Ishikawa Cells

Improvement of endometrial receptivity is necessary for successful embryo implantation, and its impairment is associated with female infertility. In this study, we investigated the effect of the roots of Cnidium officinale Makino (CoM) on endometrial receptivity in both in vitro and in vivo model of embryo implantation. We found that CoM enhanced the adhesion of JAr cells to Ishikawa cells by stimulating expression of leukemia inhibitory factor (LIF) and integrins. In addition, blocking of LIFR using hLA or neutralization of integrins αV, β3, and β5 using antibodies significantly reduced the enhanced adhesion between JAr cell and CoM-treated Ishikawa cells, indicating that LIF and integrin play an important role in trophoblast-endometrium adhesion for embryo implantation. Furthermore, we identified that CoM significantly improved the implantation rate of blastocysts in the mouse model of RU-induced implantation failure. By collecting these results, here, we suggest that CoM has a therapeutic potential against female infertility associated with decreased endometrial receptivity.

scholarly journals Sophoridine Inhibits the Tumour Growth of Non-Small Lung Cancer by Inducing Macrophages M1 Polarisation via MAPK-Mediated Inflammatory Pathway

2021 ◽  
Vol 11 ◽  
Author(s):  
Bei Zhao ◽  
Xiaodan Hui ◽  
Hairong Zeng ◽  
Yinan Yin ◽  
Jian Huang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Tumour Growth ◽  
Therapeutic Potential ◽  
Tumour Microenvironment ◽  
Lung Cancer Cells ◽  
Mice Model ◽  
Lewis Lung Cancer

Lung cancer is one of the most common and lethal neoplasms for which very few efficacious treatments are currently available. M1-like polarised tumour-associated macrophages (TAMs) are key mediators to modulate the tumour microenvironment, which play a key role in inhibiting cancer cell growth. Sophoridine, a naturally occurring alkaloid, exerts multiple pharmacological activities including anti-tumour and anti-inflammatory activities, but it has not been characterised as a regulator of tumour microenvironment towards NSCLC. Herein, the regulatory effects of sophoridine on the polarisation of THP-1 cells into TAMs and the anti-tumour effects of sophoridine-stimulated M1 polarised macrophages towards lung cancer cells were carefully investigated both in vitro and in vivo. The results showed that sophoridine could significantly promote M1 polarisation of RAW264.7 and THP-1-derived macrophages, leading to increased expression of pro-inflammatory cytokines and the M1 surface markers CD86 via activating MAPKs signaling pathway. Further investigations showed that sophoridine-stimulated RAW264.7 and THP-1-derived M1 macrophages effectively induced cell apoptosis as well as inhibited the cell colony formation and cell proliferation in both H460 and Lewis lung cancer cells. In Lewis-bearing mice model, sophoridine (15 or 25 mg/kg) significantly inhibited the tumour growth and up-regulated the expression of CD86/F4/80 in tumour tissues. Collectively, the findings clearly demonstrate that sophoridine promoted M1-like polarisation in vitro and in vivo, suggesting that sophoridine held a great therapeutic potential for treating lung cancer.

Rationale and preclinical development of LEAF-1401 and LEAF-1701: A novel class of potent next generation antifolates.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14515-e14515
Author(s):  
Victor M. Moyo ◽  
Zhenghong Xu ◽  
Kaniz Khalifa ◽  
Nishant Gandhi ◽  
Bolin Geng ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Lines ◽  
Therapeutic Potential ◽  
Metastatic Tumor ◽  
Efflux Pumps ◽  
Resistance Mechanisms ◽  
Preclinical Development ◽  
Folate Transporters

e14515 Background: Polyglutamation of antifolates by folylpolyglutamate synthase (FPGS) greatly enhances their activity, e.g. pentaglutamated pemetrexed is 80-fold more potent at inhibiting thymidylate synthase than pemetrexed. Polyglutamated antifolates however, do not readily cross the cell membrane, due to high negative charge and molecular mass. The resulting poor intracellular bioavailability greatly limits their therapeutic potential. Gamma glutamyl hydrolase (GGH) enzyme removes the glutamate residues from polyglutamates, which then are subject to efflux pumps. Resistance to pemetrexed has been linked to downregulation of both FPGS and folate transporters and upregulation of both GGH and the efflux pumps. We have been developing a novel class of nanoliposomal polyglutamated-antifolates including: LEAF-1401; nanoliposomal gamma-L pentaglutamated antifolate LEAF-1701; nanoliposomal alpha-L pentaglutamated antifolate These were designed to address key challenges of currently used antifolates namely: Bypassing the need for intracellular endogenous FPGS Direct delivery of the much more active polyglutamates through nanoliposome technology Minimizing toxicity to normal cells Mitigating against key antifolate resistance mechanisms such as downregulation of FPGS and folate transporters, and upregulation of GGH and efflux pumps Methods: In vitro testing in cell lines and in vivo testing in mice were performed using LEAF-1701 and LEAF-1401 in various tumor types. Results: Compared to pemetrexed: In vitro, LEAF-1701 and LEAF-1401 were more potent, in various cell lines while sparing normal neutrophils, colon and liver cells. In vivo, in H292 lung cancer xenografts, treatment with LEAF-1701 improved survival to 59 days vs 39 days for pemetrexed. In A549 lung cancer mouse orthotopic models, treatment with LEAF-1401 reduced metastatic tumor burden and prevented new metastases. In vivo, in mice doses of up to 80 mg/kg IV weekly were tolerated with little impact on blood counts and chemistry. Conclusions: LEAF-1701 and LEAF-1401 are innovative new chemical entities with promising preclinical activity and improved safety profiles and are now advancing to the clinic.

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