Phenanthroline Complexation Enhances the Cytotoxic Activity of the VO-Chrysin System

Metal complexation in general improves the biological properties of ligands. We have previously measured the anticancer effects of the oxidovanadium(IV) cation with chrysin complex, VO(chrys)2. In the present study, we synthesized and characterized a new complex generated by the replacement of one chrysin ligand by phenanthroline (phen), VO(chrys)phenCl, to confer high planarity for DNA chain intercalation and more lipophilicity, giving rise to a better cellular uptake. In effect, the uptake of vanadium has been increased in the complex with phen and the cytotoxic effect of this complex proved higher in the human lung cancer A549 cell line, being involved in its mechanisms of action, the production of cellular reactive oxygen species (ROS), the decrease of the natural antioxidant compound glutathione (GSH) and the ratio GSH/GSSG (GSSG, oxidized GSH), and mitochondrial membrane damage. Cytotoxic activity studies using the non-tumorigenic HEK293 cell line showed that [VO(chrys)phenCl] exhibits selectivity action towards A549 cells after 24 h incubation. The interaction with bovine serum albumin (BSA) by fluorometric determinations showed that the complex could be carried by the protein and that the binding of the complex to BSA occurs through H-bond and van der Waals interactions.

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Synthesis and Anticancer Activity of New Hydrazide-hydrazones and Their Pd(II) Complexes

Letters in Drug Design & Discovery ◽

10.2174/1570180815666180816124102 ◽

2019 ◽

Vol 16 (5) ◽

pp. 522-532 ◽

Cited By ~ 1

Author(s):

Bedia Kocyigit-Kaymakcioglu ◽

Senem Sinem Yazici ◽

Fatih Tok ◽

Miriş Dikmen ◽

Selin Engür ◽

...

Keyword(s):

Cytotoxic Activity ◽

Anticancer Activity ◽

Cell Line ◽

Cancer Cell ◽

Cytotoxic Effect ◽

A549 Cells ◽

Cancer Cell Line ◽

Fibroblast Cell ◽

Reference Drug ◽

A549 Cancer Cell Line

Background: Hydrazones, one of the important classes of organic molecules, are pharmaceutical agents comprising –CO-NH-N=CH- group in the structure therefore and exhibiting significant biological activity. Methods: 5-Chloro-N’-[(substituted)methylidene] pyrazine-2-carbohydrazide (3a-g) and their Pd(II) complexes (4a-h) were synthesized and investigated in vitro anticancer activity on A549, Caco2 cancer and normal 3T3 fibroblast cell lines, using the MTT assay. Results: Anticancer activity screening results revealed that some compounds showed remarkable cytotoxic effect. Among them, 5-chloro-N'-[(4-hydroxyphenyl)methylidene] pyrazine-2-carbohydrazide (3c) displayed higher cytotoxic activity against A549 cancer cell line than the reference drug cisplatin. Conclusion: Compound 3c showed high cytotoxic activity against A549 cancer cell line but it showed low cytotoxic effect against normal 3T3 fibroblast cell line. Antiproliferative and antimetastatic effects of 3c were determined by the real-time monitoring of cell proliferative system (RTCA DP). The cell proliferation, metastatic and invasive activities of A549 cells were decreased due to increased concentration of 3c.

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A Novel Cytotoxic Compound From the Endolichenic Fungus, Xylaria psidii Inhabiting the Lichen, Amandinea medusulina

Natural Product Communications ◽

10.1177/1934578x20933017 ◽

2020 ◽

Vol 15 (7) ◽

pp. 1934578X2093301

Author(s):

Sinthujah Santhirasegaram ◽

Suranga R. Wickramarachchi ◽

Renuka N. Attanayake ◽

Gothamie Weerakoon ◽

Sameera Samarakoon ◽

...

Keyword(s):

Lung Cancer ◽

Cytotoxic Activity ◽

Cell Line ◽

Cancer Cell Line ◽

Lung Cancer Cell Line ◽

Human Lung Cancer ◽

Isolation And Identification ◽

Its Sequence Analysis ◽

Bioassay Guided Fractionation ◽

C Nmr

The lichen host, Amandinea medusulina, collected from mangrove habitats in Sri Lanka, and its associated endolichenic fungi were isolated and identified by rDNA-ITS sequence analysis and morphological features. One of the fungal strains frequently isolated from the lichen thalli was identified as Xylaria psidii. This study aimed at the isolation and identification of the cytotoxic compounds present in this fungus. Secondary metabolites of X. psidii were first extracted into ethyl acetate and subsequently subjected to bioassay-guided fractionation to isolate the bioactive compounds. Sulforhodamine B assay against a lung cancer (NCI-H292) cell line was used to determine the differential cytotoxic activity. Bioassay-guided fractionation led to the isolation of an active compound, SS/02/29/08, showing moderate cytotoxicity (IC50 = 27.2 µg/mL). Its structure was elucidated by IR, 1D- and 2D-NMR, and 13C-NMR spectrophotometry and MS, in combination with HRMS, 13C NMR, HSQC, HMBC, and DQF-COSY. The structure of SS/02/29/08 was determined as ( Z)-3-{(3-acetyl-2-hydroxyphenyl)diazenyl}-2,4-dihydroxybenzaldehyde and identified as a new compound. This novel compound has promising differential cytotoxic activity against human lung cancer cell line (NCI-H292).

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Lipopolysaccharide administration alters extracellular vesicles in human lung-cancer cells and mice

10.1101/2020.04.17.046367 ◽

2020 ◽

Author(s):

Leandra B. Jones ◽

Sanjay Kumar ◽

Courtnee’ R. Bell ◽

Brennetta J. Crenshaw ◽

Mamie T. Coats ◽

...

Keyword(s):

Membrane Protein ◽

Bacterial Infection ◽

Cell Line ◽

Extracellular Vesicles ◽

A549 Cells ◽

Human Lung Cancer ◽

Diagnostic Tools ◽

The Impact

AbstractExtracellular vesicles (EVs) play a fundamental role in cell and infection biology and have the potential to act as biomarkers for novel diagnostic tools. In this study, we explored the in vitro impact of bacterial lipopolysaccharide administration on a cell line that represents a target for bacterial infection in the host. Administration of lipopolysaccharide at varying concentrations to this A549 cell line caused only modest changes in cell death, but EV numbers were significantly changed. After treatment with the highest concentration of lipopolysaccharide, EVs derived from A549 cells packaged significantly less interleukin-6 and lysosomal-associated membrane protein 1. We also examined the impact of lipopolysaccharide administration on exosome biogenesis and cargo composition in BALB/c mice. Serum-isolated EVs from lipopolysaccharide-treated mice showed significantly increased lysosomal-associated membrane protein 1 and toll-like receptor 4 levels compared with EVs from control mice. In summary, this study demonstrated that EV numbers and cargo were altered using these in vitro and in vivo models of bacterial infection.

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Antioxidant Activity and In-vitro Cytotoxicity Study of Novel Dombeya wallichii (An invasive plant) against Human Lung Cancer Cell Line

International Journal of Pharmaceutical Sciences Review and Research ◽

10.47583/ijpsrr.2021.v69i02.015 ◽

2021 ◽

Vol 69 (2) ◽

Author(s):

Deepak Kumar U ◽

Nivetha L ◽

Devipriya Nisha P

Keyword(s):

Antioxidant Activity ◽

Cytotoxic Activity ◽

Cell Line ◽

Invasive Plant ◽

Chemotherapeutic Agents ◽

Human Lung Cancer ◽

Therapeutic Benefits ◽

Ic50 Value ◽

Ethanolic Extracts

Recent research is focusing on the search for new types of natural chemotherapeutic agents derived from plants which are proving to be excellent sources of new compounds. The present research article was aimed to study the antioxidant activity of ethanolic extracts of Dombeya wallichii, which is an invasive plant (Plants that do not occur naturally in a region but proliferate in the area they have been introduced into) by DPPH radical scavenging method which exhibited antioxidant activity with IC50 value of 744.04 µg /ml. The cytotoxic activity of ethanolic extracts from the leaves of Dombeya wallichii, by in-vitro cytotoxic assays like MTT against lung adenocarcinoma epithelial cell line A549 which exhibited anticancer activity with IC50 value of 2.50 µg /ml concentration. This study creates the awareness about this plant which is having potential antioxidant activity, cytotoxic activity and the outcomes propose that D. wallichii as a potential source of alternative medication drugs for treating cancer. Further research is required to find out the effective mechanisms responsible for anticancer properties and for curating the therapeutic benefits of the less explored and exploited invasive species.

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Cytotoxic and Apoptotic Effects of Novel Pyrrolo[2,3-d]Pyrimidine Derivatives Containing Urea Moieties on Cancer Cell Lines

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520618666180605082026 ◽

2019 ◽

Vol 18 (9) ◽

pp. 1303-1312 ◽

Cited By ~ 3

Author(s):

Zühal Kilic-Kurt ◽

Filiz Bakar-Ates ◽

Bahriye Karakas ◽

Özgür Kütük

Keyword(s):

Cell Cycle ◽

Cytotoxic Activity ◽

Cell Line ◽

Cancer Cell ◽

A549 Cells ◽

Cancer Cell Line ◽

Anticancer Activities ◽

Cycle Arrest ◽

Apoptotic Protein ◽

Mcf 7

Background: Pyrrolo[2,3-d]pyrimidines have been recently reported to have anticancer activities through inhibition of different targets such as, Epidermal Growth Factor Receptor (EGFR) tyrosine kinase, Janus Kinase (JAK), mitotic checkpoint protein kinase (Mps1), carbonic anhydrase, MDM-2. On the other hand, aryl urea moieties which are found in some tyrosine kinase inhibitors such as Sorafenib and Linifanib have aroused recent attention as responsible for anticancer activities. The aims of this paper are to synthesize pyrrolo[ 2,3-d]pyrimidine derivatives containing urea moiety and evaluate their anti-cancer activity against human lung cancer cell line (A549), prostate cancer cell line (PC3), human colon cancer cell line (SW480) and human breast cancer cell line (MCF-7). Methods: A series of new pyrrolo[2,3-d]pyrimidines containing urea moieties have been synthesized as Scheme 1. In vitro cytotoxicity of target compounds were evaluated against, SW480, PC3, A549 and MCF-7 human cancer cell lines using a MTT assay. In order to evaluate the mechanism of cytotoxic activity of compounds 9e, 10a and 10b, having the best cytotoxic activity, Annexin V binding assay, cell cycle analysis and western blot analysis were performed. Results: Among the target compounds, 10a (IC50 = 0.19 µM) was found to be the most potent derivative against PC3 cells. Compound 10b and 9e showed the strong cytotoxic activity against MCF-7 and A549 cells with IC50 value of 1.66 µM and 4.55 µM, respectively. Flow cytometry data suggest that the cytotoxic activity of the compounds on cancer cells might be mediated by apoptosis revealing a significant increase in the percentage of late apoptotic cells and causing a cell cycle arrest at different stages. Western blot analysis of apoptosis marker demonstrated that these compounds induce apoptosis through the intrinsic pathway. Conclusion: Compound 9e displayed the strongest cytotoxicity against A549 cancer cell line, and induced late apoptosis in A549, as confirmed by cell cycle arrest in G0/G1 phase. In addition, compound 9e reduced expression of the anti-apoptotic protein Bcl-2 and enhanced expression of the pro-apoptotic protein Bax, besides increased caspase-9 and caspase-3, as well as cleavage of PARP levels. These results suggest that compound 9e showed a cytotoxic effect in A549 cells through activation of the mitochondrial apoptotic pathway. Further studies will be undertaken in our laboratory to improve cytotoxic activity of compound 9e and to identify the biological targets of 9e which are responsible for anticancer activity.

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Resistance to discodermolide, a microtubule-stabilizing agent and senescence inducer, is 4E-BP1–dependent

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1016962108 ◽

2010 ◽

Vol 108 (1) ◽

pp. 391-396 ◽

Cited By ~ 16

Author(s):

Suzan K. Chao ◽

Juan Lin ◽

Jurriaan Brouwer-Visser ◽

Amos B. Smith ◽

Susan Band Horwitz ◽

...

Keyword(s):

Cell Line ◽

P53 Protein ◽

A549 Cells ◽

Differentially Expressed ◽

Tumor Xenograft ◽

Human Lung Cancer ◽

Stabilizing Agent ◽

Accelerated Senescence ◽

Microtubule Stabilizing Agent

Discodermolide is a microtubule-stabilizing agent that induces accelerated cell senescence. A discodermolide-resistant cell line, AD32, was generated from the human lung cancer cell line A549. We hypothesize that the major resistance mechanism in these cells is escape from accelerated senescence. AD32 cells have decreased levels of 4E-BP1 mRNA and protein, relative to the parental discodermolide-sensitive A549 cells. Lentiviral-mediated re-expression of wild-type 4E-BP1 in AD32 cells increased the proliferation rate and reverted resistance to discodermolide via restoration of discodermolide-induced accelerated senescence. Consistent with this, cell growth and response to discodermolide was confirmed in vivo using tumor xenograft models. Furthermore, reintroduction of a nonphosphorylatable mutant (Thr-37/46 Ala) of 4E-BP1 was able to partially restore sensitivity and enhance proliferation in AD32 cells, suggesting that these effects are independent of phosphorylation by mTORC1. Microarray profiling of AD32-resistant cells versus sensitive A549 cells, and subsequent unbiased gene ontology analysis, identified molecular pathways and functional groupings of differentially expressed mRNAs implicated in overcoming discodermolide-induced senescence. The most statistically significant classes of differentially expressed genes included p53 signaling, G2/M checkpoint regulation, and genes involved in the role of BRCA1 in the DNA damage response. Consistent with this, p53 protein expression was up-regulated and had increased nuclear localization in AD32 cells relative to parental A549 cells. Furthermore, the stability of p53 was enhanced in AD32 cells. Our studies propose a role for 4E-BP1 as a regulator of discodermolide-induced accelerated senescence.

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The effect of antisense oligodeoxynucleotides targeting Aurora A kinase on cell proliferation and chemosensitivity to paclitaxel in human lung cancer cell line A549

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.21147 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 21147-21147

Author(s):

R. Meng ◽

G. Wu ◽

K. Y. Yang ◽

J. Cheng

Keyword(s):

Lung Cancer ◽

Cell Line ◽

A549 Cells ◽

Cancer Cell Line ◽

Lung Cancer Cell Line ◽

Human Lung Cancer ◽

Aurora A ◽

Lung Cancer Cell ◽

Mrna And Protein Expression ◽

Cell Inhibition

21147 Background: Aurora kinases representing a family of evolutionarily conserved mitotic serine/threonine kinases have been found elevated in lung andenocarcinoma cell line A549. It is suggested that the overexpression of Aurora A contributes to the carcinogenesis, chromosomal instability (CIN), and de-differentiation of lung cancers. To address its possibility as a therapeutic target for lung cancer, we employed the antisense oligodeoxynucleotide (ASODN) technique to inhibit Aurora A expression and investegate its effect on tumor growth and cell cycle of A549, as well as the chemosensitivity of paclitaxel. Methods: Aurora A ASODN was synthesized and transfected into A549 cells by lipofectAMINE 2000.Aurora A mRNA and protein expression were examined by reverse transcription -polymerase chain reaction (RT-PCR) and Western blot respectively.Cell cycle distribution was observed by flow cytometer.MTT assay was used to evaluate cell inhibition ratio before and after transfection. Results: The proliferation of the A549 cells was inhibited by Aurora A ASODN dose and time dependently. It was also observed that the IC50 of A549 cells after 48 hours’ treatment of ASODN was about 300nmol/L and under such circumstances, the Aurora A mRNA and protein expression significantly decreased (P<0.05), along with the induction of accumulation of cells in S phase and the G2-M transition. Furhermore, cell inhibition ratio of the combination of Aurora A ASODN and paclitaxel was higher significantly than paclitaxel(P<0.05) or Aurora A ASODN alone (P<0.05). Conclusions: Inhibition of Aurora A expression can results in the suppression of cell growth and chemosensitizing activity to paclitaxel in human lung cancer cell line A549. No significant financial relationships to disclose.

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Microwave-Assisted versus Conventional Isolation of Glucosinolate Degradation Products from Lunaria annua L. and Their Cytotoxic Activity

Biomolecules ◽

10.3390/biom10020215 ◽

2020 ◽

Vol 10 (2) ◽

pp. 215 ◽

Cited By ~ 3

Author(s):

Ivica Blažević ◽

Azra Đulović ◽

Vedrana Čikeš Čulić ◽

Marijana Popović ◽

Xavier Guillot ◽

...

Keyword(s):

Cytotoxic Activity ◽

Cell Line ◽

Cancer Cell ◽

Human Lung ◽

Degradation Products ◽

Cancer Cell Line ◽

Lung Cancer Cell Line ◽

Human Lung Cancer ◽

Lung Cancer Cell ◽

Microwave Assisted

Glucosinolates (GSLs) from Lunaria annua L. seeds were analyzed qualitatively and quantitatively by their desulfo counterparts using UHPLC-DAD-MS/MS technique and by their volatile breakdown products, isothiocyanates (ITCs), using GC-MS technique. GSL breakdown products were obtained by conventional techniques (hydrodistillation in a Clevenger type apparatus (HD), CH2Cl2 extraction after myrosinase hydrolysis (EXT) for 24 h) as well as by modern techniques, microwave-assisted distillation (MAD) and microwave hydrodiffusion and gravity (MHG). Seven GSLs were identified as follows: isopropyl GSL (1), sec-butyl GSL (2), 5-(methylsulfinyl)pentyl GSL (3), 6-(methylsulfinyl)hexyl GSL (4), 5-(methylsulfanyl)pentyl GSL (5), 6-(methylsulfanyl)hexyl GSL (6), and benzyl GSL (7). Additionally, pent-4-enyl- and hex-5-enyl ITCs were detected in the volatile extracts. However, their corresponding GSLs were not detected using UHPLC-DAD-MS/MS. Thus, they are suggested to be formed during GC-MS analysis via thermolysis of 5-(methylsulfinyl)pentyl- and 6-(methylsulfinyl)hexyl ITCs, respectively. Volatile isolates were tested for their cytotoxic activity using MTT assay. EXT and MHG showed the best cytotoxic activity against human lung cancer cell line A549 during an incubation time of 72 h (IC50 18.8, and 33.5 μg/mL, respectively), and against breast cancer cell line MDA-MB-231 after 48 h (IC50 6.0 and 11.8 μg/mL, respectively). These activities can be attributed to the ITCs originating from 3 and 4.

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