scholarly journals A Novel Human Recombinant Lactoferrin Inhibits Lung Adenocarcinoma Cell Growth and Migration with No Cytotoxic Effect on Normal Human Epithelial Cells

2021 ◽  
Vol 69 (1) ◽  
Author(s):  
Paulina Olszewska ◽  
Barbara Pazdrak ◽  
Marian L. Kruzel
Keyword(s):  
Lung Cancer ◽  
Cell Growth ◽  
Lung Adenocarcinoma ◽  
Cell Viability ◽  
Cancer Cell ◽  
Cancer Cell Growth ◽  
Anticancer Effects ◽  
Adenocarcinoma Cells ◽  
Normal Human ◽  
Lung Adenocarcinoma Cells

AbstractLung cancer remains the leading cause of cancer death worldwide. Despite the recent advances in cancer treatment, only a subset of patients responds to targeted and immune therapies, and many patients developing resistance after an initial response. Lactoferrin (Lf) is a natural glycoprotein with immunomodulatory and anticancer activities. We produced a novel recombinant human Lf (rhLf) that exhibits glycosylation profile compatible with the natural hLf for potential parenteral therapeutic applications. The aim of this study was to evaluate the anticancer effects of this novel rhLf in human lung adenocarcinoma cells and its mechanisms of action. The results showed a concentration-dependent inhibition of A549 cancer cell growth in response to rhLf. Treatment with 1 mg/ml of rhLf for 24 h and 72 h resulted in a significant inhibition of cancer cell growth by 32% and 25%, respectively. Moreover, rhLf increased fourfold the percentage of early and late apoptotic cells compared to the control. This effect was accompanied by increased levels of caspase-3 activity and cell cycle arrest at the S phase in rhLf-treated cancer cells. Furthermore, rhLf significantly attenuated A549 cell migration. Importantly, treatment of normal human bronchial epithelial (NHBE) cells with rhLf showed the cell viability and morphology comparable to the control. In contrast, chemotherapeutic etoposide induced cytotoxicity in NHBE cells and reduced the cell viability by 40%. These results demonstrate the selective anticancer effects of rhLf against lung adenocarcinoma cells without cytotoxicity on normal human cells. This study highlights a potential for clinical utility of this novel rhLf in patients with lung cancer.

scholarly journals ITRAQ-Based Proteomics Analysis of Triptolide On Human A549 Lung Adenocarcinoma Cells

2018 ◽  
Vol 45 (3) ◽  
pp. 917-934 ◽  
Author(s):  
Fangqiong Li ◽  
Dongxiao Zhao ◽  
Suwen Yang ◽  
Juan Wang ◽  
Qin Liu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Anticancer Activity ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cell Apoptosis ◽  
A549 Cells ◽  
Adenocarcinoma Cells ◽  
Lung Adenocarcinoma Cells ◽  
A549 Lung

Background/Aims: Triptolide (TP) is a diterpenoid triepoxide extracted from the traditional Chinese medical herb Tripterygium wilfordii that exerts prominent broad-spectrum anticancer activity to repress proliferation and induce cancer cell apoptosis through various molecular pathways. We previously observed that TP inhibits the progression of A549 cells and pancreatic cancer cells (PNCA-1) in vitro. However, the complex molecular mechanism underlying the anticancer activity of TP is not well understood. Methods: To explore the molecular mechanisms by which TP induces lung cancer cell apoptosis, we investigated changes in the protein profile of A549 cells treated with TP using a proteomics approach (iTRAQ [isobaric tags for relative and absolute quantitation] combined with NanoLC-MS/MS [nano liquid chromatography-mass spectrometry]). Changes in the profiles of the expressed proteins were analyzed using the bioinformatics tools OmicsBean and the Kyoto Encyclopedia of Genes and Genomes (KEGG) and were verified using western blotting. Apoptosis and cell cycle effects were analyzed using flow cytometry. Results: TP induced apoptosis in A549 cells and blocked A549 cells at the G2/M phase. Using iTRAQ technology, we observed 312 differentially expressed proteins associated in networks and implicated in different KEGG pathways. Gene Ontology (GO) analysis showed the overviews of dysregulated proteins in the biological process (BP), cell component (CC), and molecular function (MF) categories. Moreover, some candidate proteins involved in PARP1/AIF and nuclear Akt signaling pathways or metastasis processes were validated by western blotting. Conclusion: TP exerted anti-tumor activity on non-small cell lung cancer (NSCLC) A549 lung adenocarcinoma cells by dysregulating tumor-related protein expression. Herein, we provide a preliminary study of TP-related cytotoxicity on A549 cells using proteomics tools. These findings may improve the current understanding of the anti-tumor effects of TP on lung cancer cells and may reveal candidate proteins as potential targets for the treatment of lung cancer.

scholarly journals The critical role of HDAC1 activates NSCLC growth by nicotine resistance Cisplatin

2020 ◽  
Author(s):  
Ching-Yi Peng ◽  
Jia-Ping Wu
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Cell Growth ◽  
Cell Viability ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cisplatin Resistance ◽  
Critical Role ◽  
Cancer Cell Growth ◽  
Histone Deacetylase 1

AbstractNicotine is active in highly cisplatin-resistant cancer cells; however, there is little evidence for its resistant activity in lung cancer with cisplatin. Many mechanisms of cisplatin resistance have been proposed. The mechanisms of the nicotine treatment of cisplatin-resistant lung cancer for histone deacetylase 1 (HDAC1) activity is unknown. Nicotine was used to analyze cisplatin-resistant non-small cell lung cancer (NSCLC) cancer cell growth. Western blot was used to analyze cell cycle-related proteins. Cancer cell viability (cell survival) was measured with MTT assay. HDAC1 transfected NSCLC cells were used to analyze the direct binding between cytosol and nucleus distribution. Here, using cell viability and migration methods we firstly found nicotine regulated cisplatin-resistant NSCLC cells growth by targeting HDAC1. Expression of cisplatin was negatively correlated with HDAC1. And HDAC1 inhibitor, VPA, in the NSCLC cancer cells were predicted. Further experiments confirmed that HDAC1 directly targeted E2F and cisplatin. Besides, HDAC1 and cisplatin inhibited NSCLC cell growth and reduced expression of E2F and Cyclin E proteins. The use of nicotine compromised cisplatin-induced E2F suppression and cancer cell growth. NSCLC cancer cells co-transfected with nicotine and HDAC1 had a higher cell cycle proliferation. Taken all together, cisplatin interferes with DNA replication kills the cancer cell fastest proliferation; however, nicotine increased detoxification of cisplatin, inhibition of apoptosis and DNA repair, induced cisplatin resistance.

ERGIC3 Silencing Additively Enhances the Growth Inhibition of BFA on Lung Adenocarcinoma Cells

2020 ◽  
Vol 20 (1) ◽  
pp. 67-75
Author(s):  
Qiurong Zhao ◽  
Mingsong Wu ◽  
Xiang Zheng ◽  
Lei Yang ◽  
Zhimin Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Endoplasmic Reticulum ◽  
Cell Growth ◽  
Lung Adenocarcinoma ◽  
Cancer Cells ◽  
Cancer Cell ◽  
A549 Cells ◽  
Golgi Body ◽  
Lung Cancer Cell ◽  
Cancer Cell Growth

Background: Brefeldin A (BFA) has been known to induce endoplasmic reticulum stress (ERS) and Golgi body stress in cancer cells. ERGIC3 (endoplasmic reticulum-Golgi intermediate compartment 3) is a type II transmembrane protein located in the endoplasmic reticulum and Golgi body. ERGIC3 over-expression is frequently observed in cancer cells. Objective: In this study, we aim to explore whether BFA administered concurrently with ERGIC3 silencing would work additively or synergistically inhibit cancer cell growth. Methods: ERGIC3-siRNA was used to knock-down the expression of ERGIC3 and BFA was used to induce ERS in lung cancer cell lines GLC-82 and A549. Q-RT-PCR and Western Blot analysis were used to detect the expression of ERGIC3 and downstream molecules. GraphPad Prism 6 was used to quantify the data. Results: We demonstrated that silencing of ERGIC3 via siRNA effectively led to down-regulation of ERGIC3 at both mRNA and protein levels in GLC-82 and A549 cells. While BFA or ERGIC3- silencing alone could induce ERS and inhibit cell growth, the combination treatment of lung cancer cells with ERGIC3-silencing and BFA was able to additively enhance the inhibition effects of cell growth through up-regulation of GRP78 resulting in cell cycle arrest. Conclusion: ERGIC3 silencing in combination with BFA treatment could additively inhibit lung cancer cell growth. This finding might shed a light on new adjuvant therapy for lung adenocarcinoma.

USP10 inhibits lung cancer cell growth and invasion by upregulating PTEN

2017 ◽  
Vol 441 (1-2) ◽  
pp. 1-7 ◽  
Author(s):  
Jia Sun ◽  
Tianxiang Li ◽  
Yinying Zhao ◽  
Lirong Huang ◽  
Hua Sun ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Growth ◽  
Cancer Cell ◽  
Lung Cancer Cell ◽  
Cancer Cell Growth

Role of DACH1 on proliferation, invasion, and apoptosis in human lung adenocarcinoma cells

2021 ◽  
Vol 21 ◽  
Author(s):  
Junjie Yu ◽  
Ping Jiang ◽  
Ke Zhao ◽  
Zhiguo Chen ◽  
Tao Zuo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Tumor Cells ◽  
Human Lung ◽  
A549 Cells ◽  
Cancer Tissue ◽  
Lung Cancer Tissue ◽  
Adenocarcinoma Cells ◽  
Human Lung Adenocarcinoma Cells ◽  
Lung Adenocarcinoma Cells

Objective: To investigate DACH1 protein expression in lung cancer tissue and matched paracancerous tissue, and explore its effect on proliferation, invasion, and apoptosis in human lung adenocarcinoma cells (HLACs). Methods: Tumor tissue and matched paracancerous tissue was collected from 46 patients with pathologically diagnosed lung cancer. RT-PCR was perfomed to detect DACH1 mRNA expression and immunohistochemistry to measured DACH1 protein expression. To determine the effect of DACH1 on lung cancer behavior, small interfering RNA (siRNA) was used to silence DACH1 expression in A549 cells. The impact on the proliferation of tumor cells was then observed by MTT assay, changes in the invasion of tumor cells were identified using transwell chamber assay, and the effects on apoptosis in the cell line were detected using flow cytometry. Results: The expression of DACH1 mRNA and DACH1 protein were significantly decreased in lung cancer tissue versus matched paracancerous control tissue. Silencing of DACH1 expression in A549 cells significantly enhanced cell proliferation, significantly increased cell invasion and significantly reduced spontaneous apoptosis. Conclusion: DACH1 is downregulated in lung adenocarcinoma tissue. In vitro assessment shows that DACH1 functions as a tumor suppressor, suggesting its potential use as new target for lung cancer treatment.

scholarly journals FBXO22 mediates polyubiquitination and inactivation of LKB1 to promote lung cancer cell growth

2019 ◽  
Vol 10 (7) ◽  
Author(s):  
Xiao-Na Zhu ◽  
Ping He ◽  
Liang Zhang ◽  
Shuo Yang ◽  
Hui-Lin Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Growth ◽  
Cancer Cell ◽  
Lung Cancer Cell ◽  
Cancer Cell Growth

Cyclin D1 antisense RNA destabilizes pRb and retards lung cancer cell growth

1997 ◽  
Vol 273 (5) ◽  
pp. L941-L949 ◽  
Author(s):  
Barbara Driscoll ◽  
Lingtao Wu ◽  
Susan Buckley ◽  
Frederick L. Hall ◽  
Kathryn D. Anderson ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Death ◽  
Cell Growth ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cyclin D ◽  
Lung Cancer Cell ◽  
Cancer Cell Growth ◽  
Transfected Cells ◽  
The Impact

To investigate the role of cyclin D1 in the regulation of lung cancer cell growth, we created five stably transfected cell lines carrying a cyclin D1 antisense construct. The transfected cells exhibited a marked decrease in the rate of cell growth, in contrast to the original lines (A549 and NCI-H441). The expression of several cell cycle-regulating proteins, including cyclin A, the cyclin-dependent kinases (cdk) 2 and cdk4, in addition to cyclin D1 itself, was markedly decreased. The expression of one cdk inhibitor, p21WAF1/CIP1, increased in the A549-derived cell lines. A specific target of cyclin D1 activity, the growth-suppressing product of the retinoblastoma gene, pRb, exhibited decreased expression and a decreased level of phosphorylation in the transfected cells. Decreased expression of pRb due to a significant increase in its turnover rate suggested that the stability of the protein may depend on phosphorylation by cyclin D1-dependent cdk activity. In addition to the impact on pRb stability, decreased expression of cyclin D1 induced susceptibility to cell death after withdrawal of exogenous growth factors in the antisense transfected cell lines, a response that was not observed in the original cancer cell lines. We conclude that abrogation of cyclin D1 overexpression in lung cancer cells disrupts several key pathways that are required for uncontrolled cell growth and induces those that lead to cell death after growth factor deprivation. Therefore, we speculate that use of antisense cyclin D1 expression in appropriate gene vectors could be a useful method for retarding lung cancer cell growth in accessible tumors such as those of the lung epithelium.

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