Comparable Senescence Induction in Three-dimensional Human Cartilage Model by Exposure to Therapeutic Doses of X-rays or C-ions

Hamdi, Dounia Houria; Chevalier, François; Groetz, Jean-Emmanuel; Durantel, F.; Thuret, Jean‐Yves; Mann, Carl; Saintigny, Yannick

doi:10.1016/j.ijrobp.2016.02.014

Cited by 12 publications

(26 citation statements)

References 33 publications

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“…In recent years, increasing numbers of studies have been focusing on establishing methods to control cancer development, and inducing senescence in cancer cells is an effective treatment. The means to induce cancer cell senescence include inhibiting telomerase activity, ionizing radiation, and administration of certain drugs or chemicals . Several commercial anti‐cancer drugs have been found to induce cell senescence.…”

Section: Discussionmentioning

confidence: 99%

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Identification of a pyridine derivative inducing senescence in ovarian cancer cell lines via P21 activation

Shang

Ding

et al. 2017

Clin Exp Pharma Physio

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Cellular senescence is a state of irreversible cell growth arrest. Increasing evidence suggests that cellular senescence contribute to tumour suppression in vivo. However, only a few anti-cancer drugs have been discovered to induce cellular senescence. Searching for new compounds which can inhibit cancer cell growth by inducing senescence is becoming one of the most attractive research fields. To test the effects of candidate compounds on cancer cell growth, cell proliferation assays, senescence-associated β-galactosidase (SA-β-gal) staining, and flow cytometry assay were performed. Immunofluorescence, western blot, and qRT-PCR experiments were used to further study the molecular mechanisms of the candidate compounds. We demonstrated that a pyridine derivative, 4-(4-fluorophenyl)-2-phenyl-5, 6, 7, 8-tetrahydroquinoline (FPTHQ), from a pool of 46 compounds can induce senescence of ovarian cancer cells in a dose-dependent manner. FPTHQ caused growth inhibition by inducing G0/G1 cell cycle arrest in A2780 cells. Increased activities of SA-β-gal were observed in FPTHQ-treated A2780, OVCAR-3 and SKOV-3 cell lines. In addition, FPTHQ treatment increased the protein levels of MMP3 and the mRNA levels of IL-6 and IL-8 in A2780 cells, indicating the appearance of senescence-associated secretary phenotype (SASP) in the cells. Furthermore, we found that p21 was up-regulated and DNA damage was accumulated in FPTHQ-treated ovarian cancer cells. So far, our data suggest that FPTHQ can induce senescence in multiple ovarian cancer cell lines through activation of p21 signalling pathway by causing excessive DNA damage.

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Section: Discussionmentioning

confidence: 99%

“…The means to induce cancer cell senescence include inhibiting telomerase activity, ionizing radiation, and administration of certain drugs or chemicals. [33][34][35][36][37][38][39] Several commercial anti-cancer drugs have been found to induce cell senescence. Among them, doxorubicin might be one of the most intensively studied.…”

Section: Discussionmentioning

confidence: 99%

Identification of a pyridine derivative inducing senescence in ovarian cancer cell lines via P21 activation

Shang

Ding

et al. 2017

Clin Exp Pharma Physio

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“…Cellular viability and carbon ion radiosensitivity tests (clonogenicity, Western blot, cytometry, oxidative stress) made it possible to characterize the toxicity of carbon ions on healthy cartilage as well as the radiobiological response of cells from different chondrosarcoma lines. Carbon ion irradiation does not induce more senescence on such healthy tissue than irradiation with X-rays (25). In this study, biological effects measured in 2D cultures, such as the higher effectiveness of carbon ions compared to X-rays, seems over-exaggerated compared to the 3D model and the reality of clinics, especially concerning healthy tissues and primary cell analysis.…”

Section: Chondrosarcoma and Chondrocyte Modelsmentioning

confidence: 68%

Translational research in radiobiology in the framework of France HADRON national collaboration

Rodriguez-Lafrasse¹,

Saintigny²,

Chevalier³

et al. 2017

Transl. Cancer Res

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“…Hamdi and colleagues (2016) pointed out that the biologic effect exerted by C-ion beam—routinely used to treat chondrosarcoma—measured in 2D human articular chondrocyte cell culture might be overestimated compared to the clinical reality. The 3D cartilage model (3DCaM) provides more accurate results: in 3DCaM, higher linear energy transfer does not induce more senescence compared to X-rays, in contrast to the results obtained with 2D cell culture [ 23 ]. However, no data are available regarding the response of irradiated chondrocytes derived from hiPSCs.…”

Section: Resultsmentioning

confidence: 99%

Chondrocytes differentiated from human induced pluripotent stem cells: Response to ionizing radiation

2018

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PurposeData on the response of chondrocytes differentiated from hiPSCs (hiPSC-DCHs) to ionizing radiation (IR) are lacking. The aim of present study was to assess DNA damage response (DDR) mechanisms of IR-treated hiPSC-DCHs.Methods and materialsThe following IR-response characteristics in irradiated hiPSC-DCHs were assessed: 1) the kinetics of DNA DSB formation; 2) activation of major DNA repair mechanisms; 3) cell cycle changes and 4) reactive oxygen species (ROS), level of key markers of apoptosis and senescence.ResultsDNA DSBs were observed in 30% of the hiPSC-DCHs overall, and in 60% after high-dose (> 2 Gy) IR. Nevertheless, these cells displayed efficient DNA repair mechanisms, which reduced the DSBs over time until it reached 30% by activating key genes involved in homologous recombination and non-homologous end joining mechanisms. As similar to mature chondrocytes, irradiated hiPSC-DCH cells revealed accumulation of cells in G2 phase. Overall, the hiPSC-DCH cells were characterized by low levels of ROS, cPARP and high levels of senescence.ConclusionsThe chondrocyte-like cells derived from hiPSC demonstrated features characteristic of both mature chondrocytes and “parental” hiPSCs. The main difference between hiPSC-derived chondrocytes and hiPSCs and mature chondrocytes appears to be the more efficient DDR mechanism of hiPSC-DCHs. The unique properties of these cells suggest that they could potentially be used safely in regenerative medicine if these preliminary findings are confirmed in future studies.

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Comparable Senescence Induction in Three-dimensional Human Cartilage Model by Exposure to Therapeutic Doses of X-rays or C-ions

Cited by 12 publications

References 33 publications

Identification of a pyridine derivative inducing senescence in ovarian cancer cell lines via P21 activation

Identification of a pyridine derivative inducing senescence in ovarian cancer cell lines via P21 activation

Translational research in radiobiology in the framework of France HADRON national collaboration

Chondrocytes differentiated from human induced pluripotent stem cells: Response to ionizing radiation

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