Antiproliferative Potential of Medicinal Plants—an Evaluation by in Vivo, in Vitro, and in Silico Approaches
V. R. Mohan, A. Doss, P. S. Tresina in Ethnomedicinal Plants with Therapeutic Properties, 2019
A549 cell line was majorly developed in 1972 through the removal and culturing of cancerous lung tissue in the explanted tumor of 58-year-old male. A549 cells are human alveolar epithelial cells. They were squamous in nature and accountable for the diffusion of substances through the alveoli of lungs. In in vitro, they cultivate adherently as a monolayer, and in vivo, they bring tumors in athymic mice. A549 cell line were grown in monolayer culture, supplemented with 10% FBS, 1% penicillin/streptomycin in a 5% CO2 atmosphere at 37°C. Currently, enormous number of human nonsmall-cell lung cancer cell lines exists that are being used for both basic research and drug discovery. Other cell lines used are NCI-H1373, NCI-HI395, HCC827, SK-LU-1, DMS 53, DMS 79, SHP-77, SE 900, SW 1271, etc. Sangeetha et al. (2012) reported that treatment of A549 cells with extracts of P. granatum confirms the highest percentage of apoptosis with the ethyl acetate fraction of P. granatum rind extract which was shown by morphological changes, DNA fragmentation, and loss of membrane integrity that lead to the translocation of serine in the outer surface of the plasma membrane as confirmed by binding with annexin V. The results confirm cell death due to apoptotic pathway and not by necrosis. Sangeetha and Vijayalakshmi (2015) reported that P. granatum extract induces apoptosis in A549 cells by induction of nuclear condensation, fragmentation, apoptotic body formation, and flip-flop movement as evident by annexin staining.
Pharmacokinetics and Pharmacodynamics of Drugs Delivered to the Lung
Anthony J. Hickey, Sandro R.P. da Rocha in Pharmaceutical Inhalation Aerosol Technology, 2019
For the alveolar epithelial region, there is no suitable cell line available. Most of the primary alveolar epithelial cell lines arise from the alveolar type II cells (Forbes and Ehrhardt 2005). The well-known and widely used human cell line A549 is derived from a human pulmonary adenocarcinoma of a 58-year-old Caucasian man (Ehrhardt and Kim 2008; Steimer et al. 2005). This cell line lacks functional tight junctions which limits its use for absorption studies; however, the A549 cell line reveals biological characteristics of alveolar epithelial type II cells (Forbes and Ehrhardt 2005; Steimer et al. 2005). The A549 models are accepted to access pulmonary toxicity and have been used in metabolism, cytotoxicity, and gene delivery studies (Ehrhardt and Kim 2008; Steimer et al. 2005).
Cytokines and Alveolar Type II Cells
Jason Kelley in Cytokines of the Lung, 2022
Standiford and co-workers (1990) have demonstrated that A549 pulmonary epithelial cells express both IL-8 mRNA and protein in a time- and concentration-dependent manner when stimulated by either tumor necrosis factor or interleukin-1. In addition, medium conditioned by lipopolysaccharide-treated alveolar macrophages induced the expression of IL-8 mRNA by A549 epithelial cells. When the conditioned medium from the lipopolysaccharide-treated alveolar macrophages was incubated with antihuman tumor necrosis factor or IL-1β–neutralizing antibodies, IL-8 mRNA expression by A549 pulmonary epithelial cells was significantly diminished. Antihuman IL-8 antibodies significantly reduced, but did not eliminate, both IL-1β- and tumor necrosis factor-stimulated A549 pulmonary epithelial cell-derived neutrophil chemotactic activity. These studies suggest that pulmonary epithelial cells may be important in intercellular cytokine networks within the alveolus. However, the A549 cell line is an imperfect representation of the alveolar type II cell (Mason and Williams, 1980), and IL-8 mRNA expression and protein production in freshly isolated type II cells have not yet been studied.
Antimicrobial peptides: a promising strategy for lung cancer drug discovery?
Published in Expert Opinion on Drug Discovery, 2020
Farshid Zandsalimi, Sam Talaei, Mehdi Noormohammad Ahari, Shahin Aghamiri, Pourya Raee, Soheil Roshanzamiri, Fatemeh Yarian, Mojgan Bandehpour, Zeinab Zohrab Zadeh
A549 cell line, established via an explant culture of cancerous lung tissue of a 58-year-old Caucasian male patient, is one of the most typically used cell lines for the development of lung cancer therapeutic agents. Additionally, KRAS, KEAP1, KMT2 C, and FAT4 genes are mutated in A549 cells. These cells can be used as an alveolar type II pulmonary epithelial cell model in studies investigating the pharmacodynamics and pharmacokinetics of therapeutic agents. A549 cells can also be inoculated in mice to create cell line derived xenograft mouse models [55–57]. NCI-H1229 is another commonly used NSCLC cell line that is derived from cells originating lymph node. These cells cannot express the tumor suppressor p53 protein as they carry TP53 mutations (homozygous partial deletion). Furthermore, these cells can release the peptide hormone neuromedin B (NMB) [58]. EGFR-TKIs are extensively used for the treatment NSCLCs, which carry EGFR-activating mutations. However, after a month NSCLC cells inevitably obtain resistance to these drugs [59]. PC-9 cells have a mutation in the EGFR gene. As a result, these cells can be a good model for studies in which new strategies for overcoming EGFR-TKIs are investigated [60]. The NCI-H460 cell line was first developed by Gazdar and his colleagues through the culture of pleural fluid of a male patient with large cell lung cancer (a main subtype of NSCLC). These cells have high p53 mRNA expression at levels comparable to normal lung cells. It is noteworthy that DNA structure of these cells is normal [61].
The role of NF-κB and AhR transcription factors in lead-induced lung toxicity in human lung cancer A549 cells
Published in Toxicology Mechanisms and Methods, 2020
Ibraheem M. Attafi, Saleh A. Bakheet, Hesham M. Korashy
A549 cell line model has characteristic features of Type II cells of the pulmonary epithelium, including endocytic ability, metabolic properties, and lamellar bodies that consistent with the same type cells. The in vitro A549 cell line was selected in the current work as a study model for several reasons. First, the basal and inducible expression of the transcription factors AhR and NF-κB, CYP1A, and the proinflammatory cytokines and chemokines are much higher in A549 cell line compared with common normal bronchial cell line (BEAS-2B) (Döhr et al. 1997; Hukkanen et al. 2000; Hillyer et al. 2018). Second, although A549 cell line is cancerous, it is a valuable model for studying the mechanism of lung infections, asthma, and allergies. In addition, they have been extensively used with success as an experimental model for investigating the toxic effect of environmental toxicants such as heavy metals. For example, in 2018, Choi et al., has examined the combined effects of heavy metals using in vitro A549 human lung cancer cells (Choi et al. 2018).
Layer-by-layer pH-sensitive nanoparticles for drug delivery and controlled release with improved therapeutic efficacy in vivo
Published in Drug Delivery, 2020
Wanfu Men, Peiyao Zhu, Siyuan Dong, Wenke Liu, Kun Zhou, Yu Bai, Xiangli Liu, Shulei Gong, Shuguang Zhang
Hexane-1,6-dioldiacrylate (HDD, 99%), 3-amino-1-propanol (AP, 99%), HA, dimethyl sulfoxide (DMSO), dichloromethane (DCM), tetrahydrofuran (THF), and chloroform were purchased from Sigma Chemical Co. (St. Louis, MO). Doxorubicin hydrochloride (DOX-HCl) was purchased from Wuhan Yuan Cheng Gong Chuang Co. Ltd (Wuhan, China). 1,2-Distearoyl-sn-glycero-3-phosphocholine (DSPC) and 1-palmitoyl-2-oleoyl-phosphatidylglycerol (POPG) and cholesterol were purchased from Avanti Polar Lipids (Alabaster, AL). Methylthiazoltetrazolium (MTT) was purchased from Sigma-Aldrich (St. Louis, MO). Dulbecco’s modified Eagle’s medium (DMEM) growth media, fetal bovine serum (FBS), trypsin, penicillin, and streptomycin, were all purchased from Invitrogen (Carlsbad, CA). Human non-small cell lung carcinoma A549 cell lines were obtained from the American Type Culture Collection (ATCC). All other chemical and biological reagents were used as received.
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