Treatment with a Small Synthetic Compound, KMU-193, induces Apoptosis in A549 Human Lung Carcinoma Cells through p53 Up-Regulation

Choi, Eun Young; Shin, Kyeong‐Cheol; Lee, Jinho; Kwon, Taeg Kyu; Kim, Shin; Park, Jong‐Wook

doi:10.7314/apjcp.2015.16.14.5883

Cited by 3 publications

(3 citation statements)

References 26 publications

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“…In agreement with our results, Xu and his coworkers have identified that Pb-induced apoptosis can be mediated through an increase of P53 in mice PC 12 cells (Xu et al 2006(Xu et al , 2008. Moreover, Tousson et al (2011) reported that Pb-exposure causes a significant increase in apoptotic P53 protein in rabbit liver tissues (Tousson et al 2011) and that P53 knockdown attenuates apoptosis induction (Jung et al 2012;Choi et al 2015;Liu et al 2015). These observations not only indicate that Pb is a strong trigger for apoptosis but also strongly suggest that P53 plays a key role in Pb-induced apoptosis.…”

Section: Discussionsupporting

confidence: 92%

The role of NF-κB and AhR transcription factors in lead-induced lung toxicity in human lung cancer A549 cells

Attafi

Bakheet

Korashy

2019

Toxicology Mechanisms and Methods

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Lead (Pb) is recognized as the first heavy metal of the top six toxic air pollutants threatening human health and the second hazardous substance. Pb exposure is associated with lung impairment and high incidences of lung cancer. Nuclear factor kappa B (NF-jB) and aryl hydrocarbon receptor (AhR) signaling pathways are known to be expressed and play an important role in the lung. However, the link between Pb lung toxicity and NF-jB and/or AhR pathways remains unclear. This study was established to explore the role of NF-jB and AhR modulation in Pb-induced lung toxicity in human lung cancer A549 cells. In the current study, treatment of A549 cells with Pb significantly induced cell apoptosis as evidenced by increasing a) the percentage of cells underwent apoptosis determined by flow cytometry and b) p53 mRNA level. Pb treatment induced oxidative stress by a) increasing the formation of reactive oxygen species and b) decreasing GSTA1 mRNA levels. The toxic effects of Pb on the lung was associated with significant increases in NF-jB and AhR levels which was accompanied with increases in downstream targets genes, iNOS and CYP1A1, respectively. Inhibition of NF-jB or AhR either chemically using resveratrol or genetically using small interfering RNA (siRNA) significantly rescued A549 cells from Pb-mediated lung toxicity. The results clearly indicate that Pb-mediated lung toxicities are NF-jB and AhR-dependent mechanism.

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Section: Discussionsupporting

confidence: 92%

The role of NF-κB and AhR transcription factors in lead-induced lung toxicity in human lung cancer A549 cells

Attafi

Bakheet

Korashy

2019

Toxicology Mechanisms and Methods

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“…Recent studies revealed that p53/p21 pathway mediates lung cancer A549 cells apoptosis. 27 , 28 Our Western blot assay showed that the levels of p53 and p21Cip1/Waf1 were significantly augmented in the atracurium group compared with the control group ( Figure 5D and E ), suggesting that apoptotic effects on A549 cells are largely mediated through p53-dependent pathways.…”

Section: Discussionmentioning

confidence: 93%

Identifying candidate agents for lung adenocarcinoma by walking the human interactome

Sun

Zhang

Jiang

et al. 2016

OTT

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Despite recent advances in therapeutic strategies for lung cancer, mortality is still increasing. Therefore, there is an urgent need to identify effective novel drugs. In the present study, we implement drug repositioning for lung adenocarcinoma (LUAD) by a bioinformatics method followed by experimental validation. We first identified differentially expressed genes between LUAD tissues and nontumor tissues from RNA sequencing data obtained from The Cancer Genome Atlas database. Then, candidate small molecular drugs were ranked according to the effect of their targets on differentially expressed genes of LUAD by a random walk with restart algorithm in protein–protein interaction networks. Our method identified some potentially novel agents for LUAD besides those that had been previously reported (eg, hesperidin). Finally, we experimentally verified that atracurium, one of the potential agents, could induce A549 cells death in non-small-cell lung cancer-derived A549 cells by an MTT assay, acridine orange and ethidium bromide staining, and electron microscopy. Furthermore, Western blot assays demonstrated that atracurium upregulated the proapoptotic Bad and Bax proteins, downregulated the antiapoptotic p-Bad and Bcl-2 proteins, and enhanced caspase-3 activity. It could also reduce the expression of p53 and p21Cip1/Waf1 in A549 cells. In brief, the candidate agents identified by our approach may provide greater insights into improving the therapeutic status of LUAD.

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“…p53 is a tumor-suppressor and has been shown to mediate a variety of antiproliferative and/or pro-apoptotic processes in response to diverse forms of cellular stress (27,28). Studies have recently demonstrated that apoptosis of the A549 cells is accompanied by p53 upregulation (27,29) and siRNA-mediated p53 knockdown markedly reduces apoptosis of A549 cells (27), suggesting a role of p53 upregulation in cell apoptosis. It is thus speculative that an increase in phosphorylated p53 may further become a part of the aRVS extract-mediated anticancer effects on A549 cells.…”

Section: Discussionmentioning

confidence: 99%

Growth inhibitory and apoptosis-inducing effects of allergen-free Rhus verniciflua Stokes extract on A549 human lung cancer cells

Jang

Park

et al. 2016

Oncology Reports

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Abstract. Evidence suggests that Rhus verniciflua Stokes (RVS) or its extract has the potential to be used for the treatment of inflammatory and neoplastic diseases. However, direct use of RVS or its extract as a herbal medicine has been limited due to the presence of urushiol, an allergenic toxin. In the present study, we prepared an extract of the allergen-removed RVS (aRVS) based on a traditional method and investigated its inhibitory effect on the growth of various types of human cancer cells, including lung (A549), breast (MCF-7) and prostate (DU-145) cancer cell lines. Notably, among the cell lines tested, treatment with the aRVS extract strongly inhibited proliferation of the A549 cells at a 0.5 mg/ ml concentration for 24 h that was not cytotoxic to normal human dermal fibroblasts. Furthermore, aRVS extract treatment largely reduced the survival and induced apoptosis of the A549 cells. At the mechanistic levels, treatment with the aRVS extract led to the downregulation of Bcl-2 and Mcl-1 proteins, the activation of caspase-9/-3 proteins, an increase in cytosolic cytochrome c levels, the upregulation of Bax protein, an increase in phosphorylated p53 protein but a decrease in phosphorylated S6 protein in the A549 cells. Importantly, treatment with z-VAD-fmk, a pan-caspase inhibitor attenuated aRVS extract-induced apoptosis in the A549 cells. These results demonstrate firstly that aRVS extract has growth inhibitory and apoptosis-inducing effects on A549 human lung cancer cells through modulation of the expression levels and/or activities of caspases, Bcl-2, Mcl-1, Bax, p53 and S6.

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Treatment with a Small Synthetic Compound, KMU-193, induces Apoptosis in A549 Human Lung Carcinoma Cells through p53 Up-Regulation

Abstract: Despite recent advances in therapeutic strategies for lung cancer, mortality still is increasing. In the present study, we investigated the anti-cancer effects of

Cited by 3 publications

References 26 publications

The role of NF-κB and AhR transcription factors in lead-induced lung toxicity in human lung cancer A549 cells

The role of NF-κB and AhR transcription factors in lead-induced lung toxicity in human lung cancer A549 cells

Identifying candidate agents for lung adenocarcinoma by walking the human interactome

Growth inhibitory and apoptosis-inducing effects of allergen-free Rhus verniciflua Stokes extract on A549 human lung cancer cells

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