A dose- and time-dependent effect of oxythiamine on cell growth inhibition in non-small cell lung cancer

Cognitive Neurodynamics ◽

10.1007/s11571-021-09725-7 ◽

2021 ◽

Author(s):

Lin Bai ◽

Hui-li Zhu

Keyword(s):

Lung Cancer ◽

Cell Growth ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Critical Role ◽

A549 Cells ◽

Small Cell ◽

Time Dependent ◽

Dependent Manner ◽

Small Cell Lung

AbstractThe high mortality rate of non-small-cell lung cancer (NSCLC) is mostly due to the high risk of recurrence. A comprehensive understanding of proliferation mechanisms of NSCLC would remarkably contribute to blocking up the invasion and metastasis of tumor cells. In our previous study, the remarkable decreased activity of Thiamine-dependent enzymes (TDEs), involving in intermediary metabolism responsible for energy production of tumor, was found under conditions of thiamine deficiency in vivo. To explore the effect of Oxythiamine (OT), a TDEs antimetabolite, on cell growth, we co-cultured A549 cells with OT in vitro at various doses (0.1, 1, 10 and 100 μM) and time periods (6, 12, 24 and 48 h) and subsequent cell proliferation and apoptosis assays were performed respectively. Our findings demonstrated that A549 cells proliferation was significantly downregulated by OT treatment in a progressively dose as well as time dependent manner. Inhibition of TDEs resulted in antagonism of lung cancer growth by inducing cells to cease the cycle as well as apoptotic cell death. We concluded a critical role of OT, a TDEs antagonistic compound, indicating the potential target of its practical use.

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Antitumor Effect of Membrane-type PBLs on Non-Small Cell Lung Cancer Cell of ICR Mice

10.21203/rs.3.rs-104703/v1 ◽

2020 ◽

Author(s):

Junli Cao ◽

Peng Su ◽

Yuefeng Zhang ◽

Xin Wang ◽

Xiwei Lu ◽

...

Keyword(s):

Lung Cancer ◽

Synergistic Effect ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Small Cell ◽

Time Dependent ◽

Control Group ◽

Dependent Manner ◽

Small Cell Lung ◽

Icr Mice

Abstract This study aims at probing the inhibitory effect of transmembrane PBLs on non-small cell lung cancer (NSCLC) H446 cells and the potential application of PBLs on immune system of the experimental mice loaded with H446 cells. The changes of the gene expression of microRNA-25 and 223 in ICR mice with NSCLC were also investigated. Sixty ICR mice were randomly divided into experimental and control groups. The animal model was established via inoculation of NSCLC H446 cells at the hind thigh of mice. The plasmid PBLs was dissolved in saline solution and injected into the muscle of left thigh of the mice in experimental groups with different doses (0.1 mg, 0.2 mg and 0.3 mg per ICR mouse) using in situ injection method. After injection of PBLs solution, each three mice were killed at 12 h, 24 h, 36 h, and 48 h, respectively. The expression of microRNA-25 and 223 were detected by semi-quantitative reverse transcription-polymerase chain reaction. Tumor Necrosis Factor-γ (TNF-γ), Interleukelin-2 (IL-2) and Heat Shock Protein 70 (HSP70) in Bronchoalveolar Lavage Fluid (BALF) were detected by enzyme-linked immunosorbent assay. The expression of TNF-γ and IL-2 protein in lung tissue were detected by western blotting. The expression of microRNA-25 was up-regulated in the tissues and BALF with a dose- and time-dependent manner while microRNA-223 was down-regulated. The difference were statistically significant comparing the control group (P<0.05). The TNF-γ and IL-2 levels in BALF of ICR mice in experimental group were increased comparing the control group with a dose-dependent manner (P<0.05). Synergistic effect between PBLs and HSP70 was also studied. It was found that the growth of tumor was significantly suppressed after the transfection of PBLs. In the presence of PBLs, the proliferation of splenocytes and cytolysis in early phase of tumor development was significantly enhanced. Thus, such anti-tumor effect was further improved by the synergistic effect of PBLs with HSP70. The expression of microRNA-25 and 223 are associated with NSCLC in a dose- and time-dependent manner, they might be considered as potential biomarkers for early diagnosis of NSCLC.

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Up-Regulation of p53/miR-628-3p Pathway, a Novel Mechanism of Shikonin on Inhibiting Proliferation and Inducing Apoptosis of A549 and PC-9 Non–Small Cell Lung Cancer Cell Lines

Frontiers in Pharmacology ◽

10.3389/fphar.2021.766165 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jieli Pan ◽

Meiya Li ◽

Fenglin Yu ◽

Feiye Zhu ◽

Linyan Wang ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Treatment Strategies ◽

A549 Cells ◽

Direct Interaction ◽

Promoter Sequence ◽

Small Cell ◽

Dependent Manner ◽

Small Cell Lung

Shikonin (SHK) is a pleiotropic agent with remarkable cell growth inhibition activity against various cancer types, especially non–small cell lung cancer (NSCLC), but its molecular mechanism is still unclear. Our previous study found that miR-628-3p could inhibit the growth of A549 cells and induce its apoptosis. Bioinformatics analysis predicted that miR-628-3p promoter sequence contained p53 binding sites. Considering the regulatory effect of SHK on p53, we speculate that SHK may inhibit the growth and induce apoptosis of NSCLC cells by up-regulating miR-628-3p. CCK-8 and EdU assay confirmed the inhibitory effect of SHK on A549 and PC-9 cells. Meanwhile, quantitative reverse transcription–polymerase chain reaction and Western blot showed that SHK could promote the expression of p53 and miR-628-3p in a dose-dependent manner. Overexpression of p53 or miR-628-3p can inhibit the growth and promote apoptosis of A549 and PC-9 cells, while silencing p53 or miR-628-3p has the opposite effect. Dual luciferase reporting assay and ChIP (chromatin immunoprecipitation) assay further verified the direct interaction between p53 and the promoter of miR-628-3p. Gene knockdown for p53 or miR-628-3p confirmed that SHK inhibits the growth and induces apoptosis of A549 and PC-9 cells at least partly by up-regulating p53/miR-628-3p signaling pathway. Therefore, these novel findings provide an alternative approach to target p53/miR-628-3p axis and could be used for the development of new treatment strategies for NSCLC.

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Dehydroeffusol inhibits hypoxia-induced epithelial–mesenchymal transition in non-small cell lung cancer cells through the inactivation of Wnt/β-catenin pathway

Bioscience Reports ◽

10.1042/bsr20194284 ◽

2020 ◽

Vol 40 (5) ◽

Author(s):

Haitao Wei ◽

Feng Zhang ◽

Jiali Wang ◽

Min Zhao ◽

Tao Hou ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

A549 Cells ◽

Small Cell ◽

Mrna Levels ◽

Dependent Manner ◽

Normoxic Condition ◽

Small Cell Lung ◽

Mesenchymal Transition

Abstract Dehydroeffusol (DHE) is a phenanthrene compound that possesses anti-tumor activity. However, the effect of DHE on non-small cell lung cancer (NSCLC) has not been investigated previously. Therefore, the objective of our study was to explore the role of DHE in NSCLC and the underlying mechanism. Our results showed that DHE significantly inhibited the cell viability of A549 cells in a dose- and time-dependent manner under normoxic condition. Moreover, A549 cells were more sensitive to DHE under hypoxic condition compared with the A549 cells cultured in normoxic condition. Hypoxia-induced increased migration and invasion abilities were mitigated by DHE in A549 cells. Treatment of DHE caused increased E-cadherin expression and decreased N-cadherin expression in hypoxia-induced A549 cells. DHE also suppressed hypoxia-induced increase in both protein and mRNA levels of hypoxia inducible factor-1α (HIF-1α) expression in A549 cells. Furthermore, DHE inhibited hypoxia-induced activation of Wnt/β-catenin pathway in A549 cells. The inhibitory effect of DHE on hypoxia-induced EMT was reversed by LiCl, which is an activator of Wnt/β-catenin signaling pathway. In conclusion, these findings demonstrated that DHE prevented hypoxia-induced EMT in NSCLC cells by inhibiting the activation of Wnt/β-catenin pathway, suggesting that DHE might serve as a therapeutic target for the NSCLC metastasis.

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Matrine induces apoptosis via targeting CCR7 and enhances the effect of anticancer drugs in non-small cell lung cancer in vitro

Innate Immunity ◽

10.1177/1753425918800555 ◽

2018 ◽

Vol 24 (7) ◽

pp. 394-399 ◽

Cited By ~ 3

Author(s):

Jiangtao Pu ◽

Xiaojun Tang ◽

Xiang Zhuang ◽

Zhi Hu ◽

Kaiming He ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Anticancer Drugs ◽

Cell Lung Cancer ◽

Cell Apoptosis ◽

A549 Cells ◽

Small Cell ◽

Dependent Manner ◽

Small Cell Lung ◽

Gene Expressions

This study mainly investigated the effects of matrine on cell apoptosis and the effects of anticancer drugs in non-small cell lung cancer (NSCLC) cell lines (A549 and LK2 cells). The results showed that matrine (≥10 μM) caused a significant inhibition on cell viability and 10 and 100 μM matrine induced cell apoptosis via influencing p53, bax, casp3, and bcl-2 expressions in A549 cells. In addition, matrine significantly down-regulated C-C chemokine receptor type 7 (CCR7) expression, and blocking the down-regulation of CCR7 by exogenous chemokine ligand 21 (CCL21) treatment alleviated matrine-caused effects of apoptosis genes in A549 cells. The results were further validated in LK2 cells that matrine regulated apoptosis gene expressions, which were reversed by CCL21 treatment. Furthermore, matrine enhances the effects of cisplatin, 5-fluorouracil, and paclitaxel in A549 cells, and the anticancer effects exhibit a dosage-dependent manner. In summary, matrine induced cell apoptosis and enhanced the effects of anticancer drugs in NSCLC cells; the mechanism might be associated with the CCR7 signal.

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miR-101-3p sensitizes non-small cell lung cancer cells to irradiation

Open Medicine ◽

10.1515/med-2020-0044 ◽

2020 ◽

Vol 15 (1) ◽

pp. 413-423

Author(s):

Zhonghui Li ◽

Zhenjie Qu ◽

Ying Wang ◽

Meilin Qin ◽

Hua Zhang

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Line ◽

Cell Lung Cancer ◽

Formation Rate ◽

A549 Cells ◽

Small Cell ◽

Dependent Manner ◽

Small Cell Lung ◽

Survival Fraction

AbstractRecent studies have revealed that microRNAs regulate radiosensitivity of non-small cell lung cancer (NSCLC). The aim of this study was to investigate whether miR-101-3p is correlated with radiosensitivity of NSCLC. According to our results, miR-101-3p was downregulated in NSCLC tissues and cell lines. Moreover, miR-101-3p was decreased in A549 cells’ response to irradiation in a dose-dependent manner. Upregulation of miR-101-3p decreased survival fraction and colony formation rate and increased irradiation-induced apoptosis in irradiation-resistant cells, while miR-101-3p depletion had the opposite effects in irradiation-sensitive cells. Furthermore, mechanistic target of rapamycin (mTOR) is a target gene of miR-101-3p. The expressions of mTOR, p-mTOR, and p-S6 were curbed by overexpression of miR-101-3p in A549R cells, which was enhanced by repression of miR-101-3p in A549 cells. Intriguingly, elevation in mTOR abated miR-101-3p upregulation-induced increase in irradiation sensitivity in irradiation-resistant cell line. In contrast, rapamycin undermined miR-101-3p inhibitor-mediated reduction of irradiation sensitivity in irradiation-sensitive cell line. Besides, miR-101-3p overexpression enhanced the efficacy of radiation in an NSCLC xenograft mouse model. In conclusion, miR-101-3p sensitized A549 cells to irradiation via inhibition of mTOR-signaling pathway.

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GDC-0349 inhibits non-small cell lung cancer cell growth

Cell Death and Disease ◽

10.1038/s41419-020-03146-w ◽

2020 ◽

Vol 11 (11) ◽

Author(s):

Han Yang ◽

Jun Zhao ◽

Mengjing Zhao ◽

Lihao Zhao ◽

Li-na Zhou ◽

...

Keyword(s):

Lung Cancer ◽

Cell Growth ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Cell Apoptosis ◽

A549 Cells ◽

Small Cell ◽

Nsclc Cell ◽

Small Cell Lung ◽

Jnk Activation

Abstract Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related human mortality with a clear need for new therapeutic intervention. GDC-0349 is a potent and selective ATP-competitive mTOR inhibitor. In A549 cells and primary human NSCLC cells, GDC-0349 inhibited cell growth, proliferation, cell cycle progression, migration and invasion, while inducing significant apoptosis activation. Although GDC-0349 blocked Akt-mTORC1/2 activation in NSCLC cells, it also exerted cytotoxicity in Akt1-knockout A549 cells. Furthermore, restoring Akt-mTOR activation by a constitutively-active Akt1 only partially attenuated GDC-0349-induced A549 cell apoptosis, indicating the existence of Akt-mTOR-independent mechanisms. In NSCLC cells GDC-0349 induced sphingosine kinase 1 (SphK1) inhibition, ceramide accumulation, JNK activation and oxidative injury. Conversely, N-acetylcysteine, the JNK inhibitor and sphingosine 1-phosphate alleviated GDC-0349-induced NSCLC cell apoptosis. In vivo, daily oral administration of GDC-0349 potently inhibited NSCLC xenograft growth in mice. Akt-mTOR in-activation, SphK1 inhibition, JNK activation and oxidative stress were detected in NSCLC xenograft tissues with GDC-0349 administration. In summary, GDC-0349 inhibits NSCLC cell growth via Akt-mTOR-dependent and Akt-mTOR-independent mechanisms.

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Phanginin R Induces Cytoprotective Autophagy via JNK/c-Jun Signaling Pathway in Non-Small Cell Lung Cancer A549 Cells

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520620666200414095828 ◽

2020 ◽

Vol 20 (8) ◽

pp. 982-988 ◽

Cited By ~ 1

Author(s):

Le-Le Zhang ◽

Han Bao ◽

Yu-Lian Xu ◽

Xiao-Ming Jiang ◽

Wei Li ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Signaling Pathway ◽

Cell Lung Cancer ◽

Biological Activities ◽

A549 Cells ◽

Immunofluorescence Assay ◽

Small Cell ◽

Autophagic Flux ◽

Small Cell Lung

Background: Cassane-type diterpenoids are widely distributed in the medical plants of genus Caesalpinia. To date, plenty of cassane diterpenoids have been isolated from the genus Caesalpinia, and some of them were documented to exhibit multiple biological activities. However, the effects of these compounds on autophagy have never been reported. Objective: To investigate the effects and mechanisms of the cassane diterpenoids including Phanginin R (PR) on autophagy in Non-Small Cell Lung Cancer (NSCLC) A549 cells. Methods: Western blot analysis and immunofluorescence assay were performed to investigate the effects of the compounds on autophagic flux in A549 cells. The pathway inhibitor and siRNA interference were used to investigate the mechanism of PR. MTT assay was performed to detect cell viability. Results: PR treatment upregulated the expression of phosphatidylethanolamine-modified microtubule-associated protein Light-Chain 3 (LC3-II) in A549 cells. Immunofluorescence assay showed that PR treatment increased the production of red-fluorescent puncta in mRFP-GFP-LC3 plasmid-transfected cells, indicating PR promoted autophagic flux in A549 cells. PR treatment activated the c-Jun N-terminal Kinase (JNK) signaling pathway while it did not affect the classical Akt/mammalian Target of Rapamycin (mTOR) pathway. Pretreatment with the JNK inhibitor SP600125 or siRNA targeting JNK or c-Jun suppressed PR-induced autophagy. In addition, cotreatment with the autophagy inhibitor Chloroquine (CQ) or inhibition of the JNK/c-Jun signaling pathway increased PR-induced cytotoxicity. Conclusion: PR induced cytoprotective autophagy in NSCLC A549 cells via the JNK/c-Jun signaling pathway, and autophagy inhibition could further improve the anti-cancer potential of PR.

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NUSAP1 knockdown inhibits cell growth and metastasis of non‐small‐cell lung cancer through regulating BTG2/PI3K/Akt signaling

Journal of Cellular Physiology ◽

10.1002/jcp.29282 ◽

2019 ◽

Vol 235 (4) ◽

pp. 3886-3893 ◽

Cited By ~ 3

Author(s):

ZheYuan Xu ◽

Yang Wang ◽

Jian Xiong ◽

FengXian Cui ◽

Lan Wang ◽

...

Keyword(s):

Lung Cancer ◽

Cell Growth ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Akt Signaling ◽

Small Cell ◽

Small Cell Lung

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Silibinin Regulates Tumor Progression and Tumorsphere Formation by Suppressing PD-L1 Expression in Non-Small Cell Lung Cancer (NSCLC) Cells

Cells ◽

10.3390/cells10071632 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1632

Author(s):

Alexis Rugamba ◽

Dong Young Kang ◽

Nipin Sp ◽

Eun Seong Jo ◽

Jin-Moo Lee ◽

...

Keyword(s):

Lung Cancer ◽

Growth Factor ◽

Small Cell Lung Cancer ◽

Anticancer Activity ◽

Cell Lung Cancer ◽

Small Cell ◽

Migration And Invasion ◽

Dependent Manner ◽

Molecular Signaling ◽

Small Cell Lung

Recently, natural compounds have been used globally for cancer treatment studies. Silibinin is a natural compound extracted from Silybum marianum (milk thistle), which has been suggested as an anticancer drug through various studies. Studies on its activity in various cancers are undergoing. This study demonstrated the molecular signaling behind the anticancer activity of silibinin in non-small cell lung cancer (NSCLC). Quantitative real-time polymerase chain reaction and Western blotting analysis were performed for molecular signaling analysis. Wound healing assay, invasion assay, and in vitro angiogenesis were performed for the anticancer activity of silibinin. The results indicated that silibinin inhibited A549, H292, and H460 cell proliferation in a concentration-dependent manner, as confirmed by the induction of G0/G1 cell cycle arrest and apoptosis and the inhibition of tumor angiogenesis, migration, and invasion. This study also assessed the role of silibinin in suppressing tumorsphere formation using the tumorsphere formation assay. By binding to the epidermal growth factor receptor (EGFR), silibinin downregulated phosphorylated EGFR expression, which then inhibited its downstream targets, the JAK2/STAT5 and PI3K/AKT pathways, and thereby reduced matrix metalloproteinase, PD-L1, and vascular endothelial growth factor expression. Binding analysis demonstrated that STAT5 binds to the PD-L1 promoter region in the nucleus and silibinin inhibited the STAT5/PD-L1 complex. Altogether, silibinin could be considered as a candidate for tumor immunotherapy and cancer stem cell-targeted therapy.

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