scholarly journals Terpinen-4-ol Induces Apoptosis in Human Nonsmall Cell Lung Cancer In Vitro and In Vivo

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Chieh-Shan Wu ◽  
Yun-Ju Chen ◽  
Jeremy J. W. Chen ◽  
Jeng-Jer Shieh ◽  
Chia-Hsin Huang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Lung Cancer ◽  
Molecular Mechanisms ◽  
A549 Cells ◽  
Annexin V ◽  
Nonsmall Cell Lung Cancer ◽  
Antitumor Effects ◽  
Apoptotic Pathway

Terpinen-4-ol, a monoterpene component of the essential oils of several aromatic plants, exhibits antitumor effects. In this study, the antitumor effects of terpinen-4-ol and the cellular and molecular mechanisms responsible for it were evaluated and studied, respectively on human nonsmall cell lung cancer (NSCLC) cells. Our results indicated that terpinen-4-ol elicited a dose-dependent cytotoxic effect, as determined by MTT assay. Increased sub-G1 population and annexin-V binding, activation of caspases 9 and 3, cleavage of poly(ADPribose) polymerase (PARP), and a decrease of mitochondrial membrane potential (MMP) indicated involvement of the mitochondrial apoptotic pathway in terpinen-4-ol-treated A549 and CL1-0 cells. Elevation of the Bax/Bcl-2 ratio and a decrease in IAP family proteins XIAP and survivin were also observed following terpinen-4-ol treatment. Notably, terpinen-4-ol was able to increase p53 levels in A549 and CL1-0 cells. Diminution of p53 by RNA interference induced necrosis instead of apoptosis in A549 cells following terpinen-4-ol treatment, indicating that terpinen-4-ol-elicited apoptosis is p53-dependent. Moreover, intratumoral administration of terpinen-4-ol significantly suppressed the growth of s.c. A549 xenografts by inducing apoptosis, as confirmed by TUNEL assay. Collectively, these data provide insight into the molecular mechanisms underlying terpinen-4-ol-induced apoptosis in NSCLC cells, rendering this compound a potential anticancer drug for NSCLC.

scholarly journals PPy@Fe3O4 Nanoparticles Inhibit Tumor Growth and Metastasis Through Chemodynamic and Photothermal Therapy in Non-small Cell Lung Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Danruo Fang ◽  
Hansong Jin ◽  
Xiulin Huang ◽  
Yongxin Shi ◽  
Zeyu Liu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Photothermal Therapy ◽  
Synergistic Effects ◽  
A549 Cells ◽  
Small Cell ◽  
Small Cell Lung

Non-small cell lung cancer (NSCLC) is considered to be a principal cause of cancer death across the world, and nanomedicine has provided promising alternatives for the treatment of NSCLC in recent years. Photothermal therapy (PTT) and chemodynamic therapy (CDT) have represented novel therapeutic modalities for cancer treatment with excellent performance. The purpose of this research was to evaluate the effects of PPy@Fe3O4 nanoparticles (NPs) on inhibiting growth and metastasis of NSCLC by combination of PTT and CDT. In this study, we synthesized PPy@Fe3O4 NPs through a very facile electrostatic absorption method. And we detected reactive oxygen species production, cell apoptosis, migration and protein expression in different groups of A549 cells and established xenograft models to evaluate the effects of PPy@Fe3O4 NPs for inhibiting the growth of NSCLC. The results showed that the PPy@Fe3O4 NPs had negligible cytotoxicity and could efficiently inhibit the cell growth and metastasis of NSCLC in vitro. In addition, the PPy@Fe3O4 NPs decreased tumor volume and growth in vivo and endowed their excellent MRI capability of observing the location and size of tumor. To sum up, our study displayed that the PPy@Fe3O4 NPs had significant synergistic effects of PTT and CDT, and had good biocompatibility and safety in vivo and in vitro. The PPy@Fe3O4 NPs may be an effective drug platform for the treatment of NSCLC.

scholarly journals Antitumor Activity of DFX117 by Dual Inhibition of c-Met and PI3Kα in Non-Small Cell Lung Cancer

Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 627 ◽  
Author(s):  
Yanhua Fan ◽  
Huaiwei Ding ◽  
Donghwa Kim ◽  
Duc-Hiep Bach ◽  
Ji-Young Hong ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Antitumor Activity ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Pik3ca Mutation ◽  
A549 Cells ◽  
Small Cell ◽  
Small Cell Lung

Aberrant activation of hepatocyte growth factor (HGF)/c-Met signaling pathway caused by gene amplification or mutation plays an important role in tumorigenesis. Therefore, c-Met is considered as an attractive target for cancer therapy and c-Met inhibitors have been developed with great interests. However, cancers treated with c-Met inhibitors inevitably develop resistance commonly caused by the activation of PI3K/Akt signal transduction pathway. Therefore, the combination of c-Met and PI3Kα inhibitors showed synergistic activities, especially, in c-Met hyperactivated and PIK3CA-mutated cells. In our previous study, we rationally designed and synthesized DFX117(6-(5-(2,4-difluorophenylsulfonamido)-6-methoxypyridin-3-yl)-N-(2-morpholinoethyl) imidazo[1,2-a]pyridine-3-carboxamide) as a novel PI3Kα selective inhibitor. Herein, the antitumor activity and underlying mechanisms of DFX117 against non-small cell lung cancer (NSCLC) cells were evaluated in both in vitro and in vivo animal models. Concurrent targeted c-Met and PI3Kα by DFX117 dose-dependent inhibited the cell growth of H1975 cells (PIK3CA mutation and c-Met amplification) and A549 cells (KRAS mutation). DFX117 subsequently induced G0/G1 cell cycle arrest and apoptosis. These data highlight the significant potential of DFX117 as a feasible and efficacious agent for the treatment of NSCLC patients.

scholarly journals Engineered exosomes loaded with miR-449a selectively inhibit the growth of homologous non-small cell lung cancer

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Wen Zhou ◽  
Mingming Xu ◽  
Zhipeng Wang ◽  
Mingjun Yang
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Transfection Efficiency ◽  
Drug Carrier ◽  
A549 Cells ◽  
Small Cell ◽  
Small Cell Lung

AbstractAs an efficient drug carrier, exosome has been widely used in the delivery of genetic drugs, chemotherapeutic drugs, and anti-inflammatory drugs. As a genetic drug carrier, exosomes are beneficial to improve transfection efficiency and weaken side effects at the same time. Here, we use genetic engineering to prepare engineered exosomes (miR-449a Exo) that can actively deliver miR-449a. It was verified that miR-449a Exo had good homology targeting capacity and was specifically taken up by A549 cells. Moreover, miR-449a Exo had high delivery efficiency of miR-449a in vitro and in vivo. We demonstrated that miR-449a Exo effectively inhibited the proliferation of A549 cells and promoted their apoptosis. In addition, miR-449a Exo was found to control the progression of mouse tumors and prolong their survival in vivo. Our research provides new ideas for exosomes to efficiently and actively load gene drugs, and finds promising methods for the treatment of non-small cell lung cancer.

scholarly journals MicroRNA-421 confers paclitaxel resistance by binding to the KEAP1 3′UTR and predicts poor survival in non-small cell lung cancer

2019 ◽  
Vol 10 (11) ◽  
Author(s):  
Fu-Gang Duan ◽  
Mei-Fang Wang ◽  
Ya-Bing Cao ◽  
Dan Li ◽  
Run-Ze Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Patients ◽  
Cell Lung Cancer ◽  
A549 Cells ◽  
Small Cell ◽  
Small Cell Lung ◽  
Lung Cancer Patients

Abstract MicroRNAs regulate post-transcriptional gene expression and play important roles in multiple cellular processes. In this study, we found that miR-421 suppresses kelch-like ECH-associated protein 1(KEAP1) expression by targeting its 3′-untranslated region (3′UTR). A Q-PCR assay demonstrated that miR-421 is overexpressed in non-small cell lung cancer (NSCLC), especially in A549 cells. Consistently, the level of miR-421 was higher in clinical blood samples from lung cancer patients than in those from normal healthy donors, suggesting that miR-421 is an important lung cancer biomarker. Interestingly, overexpression of miR-421 reduced the level of KEAP1 expression, which further promoted lung cancer cell migration and invasion, as well as inhibited cell apoptosis both in vivo and in vitro. Furthermore, knockdown of miR-421 expression with an antisense morpholino oligonucleotide (AMO) increased ROS levels and treatment sensitivity to paclitaxel in vitro and in vivo, indicating that high miR-421 expression may at least partly account for paclitaxel tolerance in lung cancer patients. To find the upstream regulator of miR-421, one of the candidates, β-catenin, was knocked out via the CRISPR/Cas9 method in A549 cells. Our data showed that inhibiting β-catenin reduced miR-421 levels in A549 cells. In addition, β-catenin upregulation enhanced miR-421 expression, indicating that β-catenin regulates the expression of miR-421 in lung cancer. Taken together, our findings reveal the critical role of miR-421 in paclitaxel drug resistance and its upstream and downstream regulatory mechanisms. Therefore, miR-421 may serve as a potential molecular therapeutic target in lung cancer, and AMOs may be a potential treatment strategy.

scholarly journals Destruxin B Isolated from Entomopathogenic FungusMetarhizium anisopliaeInduces Apoptosis via a Bcl-2 Family-Dependent Mitochondrial Pathway in Human Nonsmall Cell Lung Cancer Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Chun-Chi Wu ◽  
Tzu-Hsiu Chen ◽  
Bing-Lan Liu ◽  
Li-Chen Wu ◽  
Yung-Ching Chen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Cell Lung Cancer ◽  
Molecular Mechanisms ◽  
Apoptotic Cell ◽  
A549 Cells ◽  
Nonsmall Cell Lung Cancer ◽  
Mitochondrial Pathway ◽  
Lung Cancer Cells ◽  
Gel Chromatography

Destruxin B, isolated from entomopathogenic fungusMetarhizium anisopliae, is one of the cyclodepsipeptides with insecticidal and anticancer activities. In this study, destruxin B was extracted and purified by ion-exchange chromatography, silica gel chromatography, and semipreparative high-performance liquid chromatography. The potential anticancer effects and molecular mechanisms of destruxin B in human nonsmall cell lung cancer cell lines were characterized. Our results showed that destruxin B induced apoptotic cell death in A549 cells. This event was accompanied by the activation of caspase-2, -3, and -9. Moreover, destruxin B increased the expression level of proapoptotic molecule, PUMA, while decreased antiapoptotic molecule Mcl-1. Additionally, the translocation of Bax from cytosol to mitochondrial membrane was observed upon destruxin B treatment. Knockdown of Bax by shRNA effectively attenuated destruxin-B-triggered apoptosis in A549 cells. Interestingly, similar toxic effects and underlying mechanisms including caspase activation, upregulation of PUMA, and downregulation of Mcl-1 were also observed in a p53-null lung cancer H1299 cell line upon destruxin B treatment. Taken together, our findings suggest that destruxin-B-induced apoptosis in human nonsmall cell lung cancer cells is via a Bcl-2 family-dependent mitochondrial pathway.

scholarly journals Antitumor effects of hsa‑miR661‑3p on non‑small cell lung cancer in vivo and in vitro

2019 ◽  
Author(s):  
Jingjing Lu ◽  
Xia Gu ◽  
Fanglei Liu ◽  
Zhuanghua Rui ◽  
Ming Liu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Antitumor Effects

scholarly journals Inhibitory Effect of pH-Responsive Nanogel Encapsulating Ginsenoside CK against Lung Cancer

Polymers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1784
Author(s):  
Ziyang Xue ◽  
Rongzhan Fu ◽  
Zhiguang Duan ◽  
Lei Chi ◽  
Chenhui Zhu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Water Solubility ◽  
Drug Loading ◽  
Survival Rates ◽  
A549 Cells ◽  
Ph Responsive ◽  
Antitumor Effects ◽  
Hydrophobic Cavity

Ginsenoside CK is one of the intestinal bacterial metabolites of ginsenoside prototype saponins, such as ginsenoside Rb1, Rb2, Rc, and Rd. Poor water solubility and low bioavailability have limited its application. The nanogel carriers could specifically deliver hydrophobic drugs to cancer cells. Therefore, in this study, a nanogel was constructed by the formation of Schiff base bonds between hydrazide-modified carboxymethyl cellulose (CMC-NH2) and aldehyde-modified β-cyclodextrin (β-CD-CHO). A water-in-oil reverse microemulsion method was utilized to encapsulate ginsenoside CK via the hydrophobic cavity of β-CD. β-CD-CHO with a unique hydrophobic cavity carried out efficient encapsulation of CK, and the drug loading and encapsulation efficiency were 16.4% and 70.9%, respectively. The drug release of CK-loaded nanogels (CK-Ngs) in vitro was investigated in different pH environments, and the results showed that the cumulative release rate at pH 5.8 was 85.5% after 140 h. The methylthiazolyldiphenyl-tetrazolium bromide (MTT) toxicity analysis indicated that the survival rates of A549 cells in CK-Ngs at 96 h was 2.98% compared to that of CK (11.34%). In vivo animal experiments exhibited that the inhibitory rates of CK-Ngs against tumor volume was 73.8%, which was higher than that of CK (66.1%). Collectively, the pH-responsive nanogel prepared herein could be considered as a potential nanocarrier for CK to improve its antitumor effects against lung cancer.

scholarly journals Guaiazulene Triggers ROS-Induced Apoptosis and Protective Autophagy in Non-small Cell Lung Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Qin Ye ◽  
Li Zhou ◽  
Ping Jin ◽  
Lei Li ◽  
Shuwen Zheng ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Molecular Mechanisms ◽  
Small Cell ◽  
Autophagic Flux ◽  
Small Cell Lung ◽  
Induced Apoptosis

Non-small cell lung cancer (NSCLC) is one of the most frequent cancers worldwide, yet effective treatment remains a clinical challenge. Guaiazulene (GYZ), a cosmetic color additive, has previously been characterized as a potential antitumor agent due to observed anticancer effects. However, the efficacy of GYZ in the treatment of NSCLC and the involved molecular mechanisms remain largely unknown. Here, we indicated a role for GYZ in the suppression of NSCLC both in vitro and in vivo via triggering reactive oxygen species (ROS)-induced apoptosis. Concomitantly, GYZ induced complete autophagic flux in NSCLC cells via inhibiting the Akt/mTOR signaling pathway, which displayed cytoprotective effect against GYZ-induced growth suppression. Accompanied with autophagy inhibition obviously enhanced the effects of GYZ. Notably, GYZ acts synergistically with paclitaxel in the suppression of NSCLC in vitro. Together, our results for the first time reported that GYZ suppressed the proliferation of NSCLC and suggested a potential strategy for inhibiting NSCLC growth by combinational use of GYZ and autophagy inhibitors.

scholarly journals Effects of Laminaria Japonica Polysaccharides on the Survival of Non-Small-Cell Lung Cancer A549 Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-9
Author(s):  
Mengxing Yao ◽  
XiaoJun Qian ◽  
Houying Qin
Keyword(s):  
Lung Cancer ◽  
Protein Expression ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
A549 Cells ◽  
Small Cell ◽  
Control Group ◽  
Small Cell Lung

Objective. To investigate the effect of Laminaria japonica polysaccharides (LJP) on the survival of non-small-cell lung cancer (NSCLC) A549 cells and its mechanism. Methods. In vitro: the cells were randomly divided into control group, LJP (5 mg/ml) group, LJP (10 mg/ml) group, and LJP (20 mg/ml) group. After corresponding treatment, the survival rate and the expression of proteins related to proliferation, apoptosis, epithelial-mesenchymal transition (EMT), and signaling pathway were detected by CCK8 assay and Western blot, respectively. In vivo: a xenograft model was established to detect the tumor volume and mass and the expression of the above pathway proteins. Results. Compared with the control group, LJP decreased the survival rate of A549 cells (P<0.05), inhibited the protein expression of Ki67 and PCNA (P<0.05), downregulated the expression of Bcl-2 while upregulated the expression of Bax, cl-caspase-3, and cl-caspase-9 (P<0.05), upregulated the expression of E-cadherin, downregulated the expression of vascular endothelial growth factor (VEGF) and N-cadherin (P<0.05), and downregulated β-catenin, transcription factor-4 (TCF4), and c-Myc protein expression levels (P<0.05). In vivo: LJP decreased the volume and mass of the xenograft tumors and downregulated β-catenin, TCF4, and c-Myc protein expression levels compared with the control group (P<0.05). Conclusion. LJP can inhibit the survival of non-small-cell lung cancer A549 cells in vitro, and its mechanism is related to the inhibition of activation of β-catenin/TCF4 pathway activation.

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