scholarly journals The p53–53BP1-Related Survival of A549 and H1299 Human Lung Cancer Cells after Multifractionated Radiotherapy Demonstrated Different Response to Additional Acute X-ray Exposure

2020 ◽  
Vol 21 (9) ◽  
pp. 3342
Author(s):  
Margarita Pustovalova ◽  
Lina Alhaddad ◽  
Nadezhda Smetanina ◽  
Anna Chigasova ◽  
Taisia Blokhina ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Strand Break ◽  
Human Lung Cancer ◽  
Cancer Resistance ◽  
Cellular Mechanisms ◽  
X Ray ◽  
Γh2ax Foci ◽  
Therapeutic Benefits ◽  
Different Response ◽  
Kinetics Of

Radiation therapy is one of the main methods of treating patients with non-small cell lung cancer (NSCLC). However, the resistance of tumor cells to exposure remains the main factor that limits successful therapeutic outcome. To study the molecular/cellular mechanisms of increased resistance of NSCLC to ionizing radiation (IR) exposure, we compared A549 (p53 wild-type) and H1299 (p53-deficient) cells, the two NSCLC cell lines. Using fractionated X-ray irradiation of these cells at a total dose of 60 Gy, we obtained the survived populations and named them A549IR and H1299IR, respectively. Further characterization of these cells showed multiple alterations compared to parental NSCLC cells. The additional 2 Gy exposure led to significant changes in the kinetics of γH2AX and phosphorylated ataxia telangiectasia mutated (pATM) foci numbers in A549IR and H1299IR compared to parental NSCLC cells. Whereas A549, A549IR, and H1299 cells demonstrated clear two-component kinetics of DNA double-strand break (DSB) repair, H1299IR showed slower kinetics of γH2AX foci disappearance with the presence of around 50% of the foci 8 h post-IR. The character of H2AX phosphorylation in these cells was pATM-independent. A decrease of residual γH2AX/53BP1 foci number was observed in both A549IR and H1299IR compared to parental cells post-IR at extra doses of 2, 4, and 6 Gy. This process was accompanied with the changes in the proliferation, cell cycle, apoptosis, and the expression of ATP-binding cassette sub-family G member 2 (ABCG2, also designated as CDw338 and the breast cancer resistance protein (BCRP)) protein. Our study provides strong evidence that different DNA repair mechanisms are activated by multifraction radiotherapy (MFR), as well as single-dose IR, and that the enhanced cellular survival after MFR is reliant on both p53 and 53BP1 signaling along with non-homologous end-joining (NHEJ). Our results are of clinical significance as they can guide the choice of the most effective IR regimen by analyzing the expression status of the p53–53BP1 pathway in tumors and thereby maximize therapeutic benefits for the patients while minimizing collateral damage to normal tissue.

scholarly journals A new Pb(II)-based coordination polymer constructed from a semirigid tricarboxylate ligand: crystal structure and anti-lung cancer activity

2019 ◽  
Vol 42 (1) ◽  
pp. 8-12
Author(s):  
Kun-Ning Yang ◽  
Ke-De Yuan ◽  
Li-Li Jiang ◽  
Yong Zhang
Keyword(s):  
Lung Cancer ◽  
Coordination Polymer ◽  
Ultrasonic Method ◽  
Three Dimensional ◽  
Human Lung Cancer ◽  
X Ray Diffraction ◽  
Dioic Acid ◽  
X Ray ◽  
The One ◽  
Solvothermal Conditions

Abstract Based on a semirigid tricarboxylate ligand 5-((4-carboxyphenoxy)methyl)benzene-1,3-dioic acid (H3L), a new Pb(II)-based coordination polymer formulated as [Pb(HL)(H2O)](H2O) (1) was synthesized under solvothermal conditions and characterized by single-crystal X-ray structural analysis, power X-ray diffraction, and elemental analysis. Compound 1 is a two-dimensional layered structure formed by the connection of the one-dimensional Pb(II)-based secondary building unit chains with the partly deprotonated HL ligands, which are further extended into three-dimensional supermolecular structures through the H-bonds. Furthermore, the size of the as-prepared 1 could be downsized into the nano region through a simple ultrasonic method. Finally, the antilung cancer activities of 1 and the nanosized 1 have been probed via the MTT assay against three human lung cancer cell lines (A549, H1299, and PC9).

scholarly journals The Phenoxyphenol Compound 4-HPPP Selectively Induces Antiproliferation Effects and Apoptosis in Human Lung Cancer Cells through Aneupolyploidization and ATR DNA Repair Signaling

2020 ◽  
Vol 2020 ◽  
pp. 1-14 ◽  
Author(s):  
Wangta Liu ◽  
Chang-Yi Wu ◽  
Mei-Jei Lu ◽  
Yung-Jen Chuang ◽  
Eing-Mei Tsai ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Strand Break ◽  
Inhibitory Effect ◽  
Lung Cancer Cells ◽  
Tumor Xenograft ◽  
Human Lung Cancer ◽  
Specific Cell ◽  
Ros Scavenging

Lung cancer is a leading cause of cancer death worldwide, and non-small-cell lung cancer (NSCLC) accounts for 85% of lung cancer, which is highly metastatic, leading to the poor survival rate of patients. We recently reported that 4-[4-(4-hydroxyphenoxy)phenoxy]phenol (4-HPPP), a phenoxyphenol, exerts antihepatoma effects by inducing apoptosis and autophagy. In this study, we further examined the effect of 4-HPPP and its analogs on NSCLC cells. Colony formation assays showed that 4-HPPP exerts selective cytotoxicity against NSCLC H1299 cells; furthermore, the inhibitory effect of 4-HPPP on the proliferation and migration of NSCLC cells was validated using an in vivo zebrafish-based tumor xenograft assay. The flow cytometry-based dichlorofluorescein diacetate (DCF-DA) assays indicated that 4-HPPP caused an increase in reactive oxygen species (ROS) in NSCLC cells, and Western blot assays showed that the major ROS scavenging enzymes superoxide dismutases- (SODs-) 1/2 were upregulated, whereas peroxidase (PRX) was downregulated. Furthermore, 4-HPPP caused both aneuploidization and the accumulation of γH2AX, a sensor of DNA damage, as well as the activation of double-strand break (DSB) markers, especially Ataxia-telangiectasia-mutated and Rad3-related (ATR) in NSCLC cells. Our present work suggests that the antiproliferative effects of 4-HPPP on lung cancer cells could be due to its phenoxyphenol structure, and 4-HPPP could be a candidate molecule for treating NSCLC by modulating ROS levels and lowering the threshold of polyploidy-specific cell death in the future.

scholarly journals Anti-cancer & anti-metastasis properties of bioorganic-capped silver nanoparticles fabricated from Juniperus chinensis extract against lung cancer cells

AMB Express ◽  
2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hassan Noorbazargan ◽  
Sobhan Amintehrani ◽  
Aghigh Dolatabadi ◽  
Ainaz Mashayekhi ◽  
Nazanin Khayam ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Lung Cancer ◽  
Silver Nanoparticles ◽  
Zeta Potential ◽  
Cancer Cells ◽  
Lung Cancer Cells ◽  
Human Lung Cancer ◽  
X Ray ◽  
Juniperus Chinensis ◽  
Anti Cancer

AbstractThe current study evaluated the anti-cancer properties of bio-functionalized silver nanoparticles fabricated by Juniperus chinensis leaf extracts. The nanoparticles were characterized by scanning electron microscopy, transmission electron microscopy, UV–visible spectroscopy, Fourier transform infrared spectroscopy, X-ray diffraction, dynamic light scattering, Zeta potential and X-ray spectroscopy. Further, this study elucidated the cellular and molecular mechanisms of nanoparticles for anti-proliferative and apoptotic effects on human lung cancer cells (A549) and compared them with commercial drug cisplatin. The size of the spherical nanoparticle was 12.96 nm with negative zeta potential. Up-regulation of caspase 3,9 and p53, Annexin V-FITC/PI, DAPI staining, and ROS production indicated the remarkable apoptotic effect of AgNPs compared to cisplatin. Moreover, down-regulation of MMP2/MMP9 scratch and matrigel assays revealed anti-metastatic properties of AgNPs. Cell cycle analysis and downregulation of cyclin D1 indicated cancer cell cessation in the G0/G1 phase. Overall, the results revealed that the green-synthetized AgNPs had anti-metastasis and anti-proliferation effects on lung cancer cells in comparison to cisplatin with lower side effects on the normal cell line.

Brownian Diffusion and Surface Kinetics of Liposome and Viral Particle Uptake by Human Lung Cancer Cells In-Vitro

2006 ◽  
Vol 34 (10) ◽  
pp. 1573-1586 ◽  
Author(s):  
Donghui Zhu ◽  
S. Patrick Lennon ◽  
Michael H. Peters ◽  
Wright C. Finney ◽  
Mandip Singh
Keyword(s):  
Lung Cancer ◽  
Viral Particle ◽  
Human Lung ◽  
Human Lung Cancer ◽  
Brownian Diffusion ◽  
Surface Kinetics ◽  
Particle Uptake ◽  
Human Lung Cancer Cells ◽  
Kinetics Of

scholarly journals Metabolism of Selenite in Human Lung Cancer Cells: X-Ray Absorption and Fluorescence Studies

2011 ◽  
Vol 133 (45) ◽  
pp. 18272-18279 ◽  
Author(s):  
Claire M. Weekley ◽  
Jade B. Aitken ◽  
Stefan Vogt ◽  
Lydia A. Finney ◽  
David J. Paterson ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Human Lung ◽  
Lung Cancer Cells ◽  
Human Lung Cancer ◽  
X Ray ◽  
Fluorescence Studies ◽  
Human Lung Cancer Cells ◽  
X Ray Absorption
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