Features of senescence and cell death induced by doxorubicin in A549 cells: organization and level of selected cytoskeletal proteins

Litwiniec, Anna; Grzanka, Alina; Helmin-Basa, Anna; Gackowska, Lidia; Grzanka, Dariusz

doi:10.1007/s00432-009-0711-4

Cited by 46 publications

(50 citation statements)

References 91 publications

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“…DNA fragmentation was measured by the terminal deoxynucleotidyl transferase-mediated dUTP nickend labeling (TUNEL) method using a commercially available kit (APO-DIRECT, BD Biosciences Pharmingen), according to the manufacturer's instructions as described by Litwiniec [6].…”

Section: Methodsmentioning

confidence: 99%

“…Stress-induced premature senescence is independent of telomere length and could result from the action of anticancer drugs. There are several symptoms of senescence on the cellular level, including flattened and enlarged cell shape, increased cytoplasmic granularity, lipofuscin accumulation, enhanced senescence-associated b-galactosidase activity, as well as changes in expression of the critical cell cycle regulatory tumor suppressor genes [6][7][8][9][10]. From these genes, p53 and p16 are the most commonly mutated in different types of cancer and they are implicated in the execution of senescence program via different transduction pathway.…”

Section: Introductionmentioning

confidence: 99%

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Expression of cyclin B1 after induction of senescence and cell death in non-small cell lung carcinoma A549 cells

Żuryń

Gagat

Gackowska

et al. 2012

Folia Histochem Cytobiol.

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Abstract:The purpose of this study was to evaluate the level of mitotic cyclin B1 in the context of senescence and cell death in A549 non-small cell lung carcinoma cells. This was performed through analysis of the cell cycle, the percentage of SA-b-galactosidase-positive, as well as TUNEL-positive cells. Morphological alterations were studied using a transmission electron microscope. Changes in the intracellular level and the presence of cyclin B1 in the nucleus and cytoplasm areas were detected by flow cytometry and confocal fluorescence microscopy, respectively. In the cells exposed to various concentrations of doxorubicin, different kinds of cell death and senescent phenotype were observed. Alterations in the cell cycle and increased polyploidy may be indicative of mitotic catastrophe execution. Changes in cyclin B1 may also be strictly related to its different regulation at mitotic catastrophe and senescence programs.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Expression of cyclin B1 after induction of senescence and cell death in non-small cell lung carcinoma A549 cells

Żuryń

Gagat

Gackowska

et al. 2012

Folia Histochem Cytobiol.

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“…Senescence-associated-beta-galactosidase (SA-β-gal) staining A549 cell senescence was identified by senescence-associated β -gal staining [31] . After 60 h treatment with 5b, 5d, and 5e (80 µmol/L), cells were rinsed twice with PBS, fixed for 5 min in a solution containing formaldehyde and glutaraldehyde, and then rinsed with PBS.…”

Section: Hoechst 33258 Stainingmentioning

confidence: 99%

“…Furthermore, these compounds did not cause necrosis in A549 cells. The classical method for detecting senescence is to test for SA-β-Gal activity in cells using the substrate, X-Gal (5-bromo-4-chloro-3-indoly-β-Dgalactoside) [31] . In SA-β-Gal-stained A549 cells, senescent cells were stained blue.…”

Section: Wwwchinapharcom LI Y Et Almentioning

confidence: 99%

Novel ferrocenyl derivatives exert anti-cancer effect in human lung cancer cells in vitro via inducing G1-phase arrest and senescence

Han

et al. 2013

Acta Pharmacol Sin

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Aim: To investigate the effects of 7 novel 1-ferrocenyl-2-(5-phenyl-1H-1,2,4-triazol-3-ylthio) ethanone derivatives on human lung cancer cells in vitro and to determine the mechanisms of action. Methods: A549 human lung cancer cells were examined. Cell viability was analyzed with MTT assay. Cell apoptosis and senescence were examined using Hoechst 33258 and senescence-associated-β-galactosidase (SA-β-gal) staining, respectively. LDH release was measured using a detection kit. Cell cycle was analyzed using a flow cytometer. Intracellular ROS level was measured with the 2′,7′-dichlorodihydrofluorescein probe. Phosphorylation of p38 was determined using Western blot. Results: Compounds 5b, 5d, and 5e (40 and 80 µmol/L) caused significant decrease of A549 cell viability, while other 4 compounds had no effect on the cells. Compounds 5b, 5d, and 5e (80 µmol/L) induced G 1 -phase arrest (increased the G 1 population by 22.6%, 24.23%, and 26.53%, respectively), and markedly increased SA-β-gal-positive cells. However, the compounds did not cause nuclear DNA frag mentation and chromatin condensation in A549 cells. Nor did they affect the release of LDH from the cells. The compounds significantly elevated the intracellular ROS level, decreased the mitochondrial membrane potential, and increased p38 phosphorylation in the cells. In the presence of the antioxidant and free radical scavenger N-acetyl-L-cysteine (10 mmol/L), above effects of compounds 5b, 5d, and 5e were abolished. Conclusion: The compounds 5b, 5d, and 5e cause neither apoptosis nor necrosis of A549 cells, but exert anti-cancer effect via inducing G 1 -phase arrest and senescence through ROS/p38 MAP-kinase pathway.

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“…Abundant data support the notion that RS is a natural barrier against tumorigenesis [4,5]. Stress-induced premature senescence is a program executed by cells in response to chemotherapy, and RS induced by DNA-damaging anticancer drugs is one of the key determinants of successful chemotherapy [6].…”

Section: Introductionmentioning

confidence: 99%

Doxorubicin anti-tumor mechanisms include Hsp60 post-translational modifications leading to the Hsp60/p53 complex dissociation and instauration of replicative senescence

et al. 2017

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a b s t r a c tThe chaperone Hsp60 is pro-carcinogenic in certain tumor types by interfering with apoptosis and with tumor cell death. In these tumors, it is not yet known whether doxorubicin anti-tumor effects include a blockage of the pro-carcinogenic action of Hsp60. We found a doxorubicin dose-dependent viability reduction in a human lung mucoepidermoid cell line that was paralleled by the appearance of cell senescence markers. Concomitantly, intracellular Hsp60 levels decreased while its acetylation levels increased. The data suggest that Hsp60 acetylation interferes with the formation of the Hsp60/p53 complex and/or promote its dissociation, both causing an increase in the levels of free p53, which can then activate the p53-dependent pathway toward cell senescence. On the other hand, acetylated Hsp60 is ubiquitinated and degraded and, thus, the anti-apoptotic effect of the chaperonin is abolished with subsequent tumor cell death. Our findings could help in the elucidation of the molecular mechanisms by which doxorubicin counteracts carcinogenesis and, consequently, it would open new roads for the development of cancer treatment protocols targeting Hsp60.

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Features of senescence and cell death induced by doxorubicin in A549 cells: organization and level of selected cytoskeletal proteins

Cited by 46 publications

References 91 publications

Expression of cyclin B1 after induction of senescence and cell death in non-small cell lung carcinoma A549 cells

Expression of cyclin B1 after induction of senescence and cell death in non-small cell lung carcinoma A549 cells

Novel ferrocenyl derivatives exert anti-cancer effect in human lung cancer cells in vitro via inducing G1-phase arrest and senescence

Doxorubicin anti-tumor mechanisms include Hsp60 post-translational modifications leading to the Hsp60/p53 complex dissociation and instauration of replicative senescence

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