Genetic stability of pluripotent stem cells during anti-cancer therapies

Suchorska, Wiktoria Maria; Augustyniak, Ewelina; Łukjanow, Magdalena

doi:10.3892/etm.2016.2993

Cited by 9 publications

(8 citation statements)

References 82 publications

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“…Graphene oxide treatment showed dose-dependent effects on 8-OH-dG concentrations, whereas untreated cells showed no significant levels of 8-OH-dG (Figure 7A). Under certain threshold conditions, genomic instability can be attenuated through DNA replication-coupled repair mechanisms, whereas more sensitive cells, such as germ and stem cells, may be redirected to cell cycle arrest and apoptosis [55]. However, the molecular mechanisms of genotoxicity and cytotoxicity remain unclear.…”

Section: Resultsmentioning

confidence: 99%

Evaluation of Graphene Oxide Induced Cellular Toxicity and Transcriptome Analysis in Human Embryonic Kidney Cells

et al. 2019

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Graphene, a two-dimensional carbon sheet with single-atom thickness, shows immense promise in several nanoscientific and nanotechnological applications, including in sensors, catalysis, and biomedicine. Although several studies have shown the cytotoxicity of graphene oxide in different cell types, there are no comprehensive studies on human embryonic kidney (HEK293) cells that include transcriptomic analysis and an in vitro investigation into the mechanisms of cytotoxicity following exposure to graphene oxide. Therefore, we exposed HEK293 cells to different concentrations of graphene oxide for 24 h and performed several cellular assays. Cell viability and proliferation assays revealed a significant dose-dependent cytotoxic effect on HEK293 cells. Cytotoxicity assays showed increased lactate dehydrogenase (LDH) leakage and reactive oxygen species (ROS) generation, and decreased levels of reduced glutathione (GSH) and increased level of oxidized glutathione indicative of oxidative stress. This detailed mechanistic approach showed that graphene oxide exposure elicits significant decreases in mitochondrial membrane potential and ATP synthesis, as well as in DNA damage and caspase 3 activity. Furthermore, our RNA-Seq analysis revealed that HEK293 cells exposed to graphene oxide significantly altered the expression of genes involved in multiple apoptosis-related biological pathways. Moreover, graphene oxide exposure perturbed the expression of key transcription factors, promoting these apoptosis-related pathways by regulating their downstream genes. Our analysis provides mechanistic insights into how exposure to graphene oxide induces changes in cellular responses and massive cell death in HEK293 cells. To our knowledge, this is the first study describing a combination of cellular responses and transcriptome in HEK293 cells exposed to graphene oxide nanoparticles, providing a foundation for understanding the molecular mechanisms of graphene oxide-induced cytotoxicity and for the development of new therapeutic strategies.

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Section: Resultsmentioning

confidence: 99%

Evaluation of Graphene Oxide Induced Cellular Toxicity and Transcriptome Analysis in Human Embryonic Kidney Cells

et al. 2019

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“…The human telomeric sequence is composed of hexamer repeats (5'-TTAGGG-3') at the 3' end strand. Human telomeres have ~500 to 2,000 copies of hexamer repetitions, giving rise to 3,000 to 12,000 base pairs (8)(9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

hTERT C250T promoter mutation and telomere length as a molecular markers of cancer progression in patients with head and neck cancer

Barczak

Suchorska

Sobecka

et al. 2017

Molecular Medicine Reports

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Squamous cell carcinoma of the head and neck (HNSCC) is the sixth leading cause of cancer worldwide, representing over half a million incidents every year. Cancer cells, including HNSCC, are characterized by increased telomerase activity. This enzymatic complex is active in ~90% of all cancer types and is responsible for the lengthening of telomeres. Highly recurrent point mutations in the human telomerase reverse transcriptase (hTERT) promoter have recently been reported in a number of human neoplasms. The aim of the present study was to analyze the prevalence of the hTERT promoter C250T mutation and telomere length in the blood leukocytes of 61 patients with HNSCC and 49 healthy individuals. Quantitative polymerase chain reaction identified the hTERT promoter mutation in 36% of patients with HNSCC. To the best of our knowledge this is first report indicating the presence of shorter telomeres in early stage tumors. In addition, the results suggest that the C250T hTERT promoter mutation and telomere length assessment may serve as important molecular markers of HNSCC progression.

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“…This is important because undifferentiated cells differ greatly from differentiated cells in numerous aspects, including the course of the cell cycle, metabolic profile, initial level of reactive oxygen species, capacity for DNA repair, apoptosis and the frequency of de novo mutations (8). In addition, hESCs and hiPSCs differ in terms of genotypes and phenotypes (9).…”

Section: Introductionmentioning

confidence: 99%

Comparison of the early response of human embryonic stem cells and human induced pluripotent stem cells to ionizing radiation

Suchorska

Augustyniak

Łukjanow

2017

Molecular Medicine Reports

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Despite the well-demonstrated efficacy of stem cell (SC) therapy, this approach has a number of key drawbacks. One important concern is the response of pluripotent SCs to treatment with ionizing radiation (IR), given that SCs used in regenerative medicine will eventually be exposed to IR for diagnostic or treatment-associated purposes. Therefore, the aim of the present study was to examine and compare early IR-induced responses of pluripotent SCs to assess their radioresistance and radiosensitivity. In the present study, 3 cell lines; human embryonic SCs (hESCs), human induced pluripotent SCs (hiPSCs) and primary human dermal fibroblasts (PHDFs); were exposed to IR at doses ranging from 0 to 15 gray (Gy). Double strand breaks (DSBs), and the gene expression of the following DNA repair genes were analyzed: P53; RAD51; BRCA2; PRKDC; and XRCC4. hiPSCs demonstrated greater radioresistance, as fewer DSBs were identified, compared with hESCs. Both pluripotent SC lines exhibited distinct gene expression profiles in the most common DNA repair genes that are involved in homologous recombination, non-homologous end-joining and enhanced DNA damage response following IR exposure. Although hESCs and hiPSCs are equivalent in terms of capacity for pluripotency and differentiation into 3 germ layers, the results of the present study indicate that these 2 types of SCs differ in gene expression following exposure to IR. Consequently, further research is required to determine whether hiPSCs and hESCs are equally safe for application in clinical practice. The present study contributes to a greater understanding of DNA damage response (DDR) mechanisms activated in pluripotent SCs and may aid in the future development of safe SC-based clinical protocols.

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Genetic stability of pluripotent stem cells during anti-cancer therapies

Cited by 9 publications

References 82 publications

Evaluation of Graphene Oxide Induced Cellular Toxicity and Transcriptome Analysis in Human Embryonic Kidney Cells

Evaluation of Graphene Oxide Induced Cellular Toxicity and Transcriptome Analysis in Human Embryonic Kidney Cells

hTERT C250T promoter mutation and telomere length as a molecular markers of cancer progression in patients with head and neck cancer

Comparison of the early response of human embryonic stem cells and human induced pluripotent stem cells to ionizing radiation

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