Transient Alteration of Cellular Redox Buffering before Irradiation Triggers Apoptosis in Head and Neck Carcinoma Stem and Non-Stem Cells

Background: Head and neck squamous cell carcinoma (HNSCC) is an aggressive and recurrent malignancy owing to intrinsic radioresistance and lack of induction of apoptosis. The major focus of this work was to design a transient glutathione depleting strategy during the course of irradiation of HNSCC in order to overcome their radioresistance associated with redox adaptation. Methodology/Principal Findings: Treatment of SQ20B cells with dimethylfumarate (DMF), a GSH-depleting agent, and L-Buthionine sulfoximine (BSO), an inhibitor of GSH biosynthesis 4 h before a 10 Gy irradiation led to the lowering of the endogenous GSH content to less than 10 % of that in control cells and to the triggering of radiation-induced apoptotic cell death. The sequence of biochemical events after GSH depletion and irradiation included ASK-1 followed by JNK activation which resulted in the triggering of the intrinsic apoptotic pathway through Bax translocation to mitochondria. Conclusions: This transient GSH depletion also triggered radiation-induced cell death in SQ20B stem cells, a key event to overcome locoregional recurrence of HNSCC. Finally, our in vivo data highlight the relevance for further clinical trials o

Biological Effects of Space Radiation on Human Cells: History, Advances and Outcomes

Exposure to radiation is one of the main concerns for space exploration by humans. By focusing deliberately on the works performed on human cells, we endeavored to review, decade by decade, the technological developments and conceptual advances of space radiation biology. Despite considerable efforts, the cancer and the toxicity risks remain to be quantified: 1) the nature and the frequency of secondary heavy ions need to be better characterized in order to estimate their contribution to the dose and to the final biological response; 2) the diversity of radiation history of each astronaut and the impact of individual susceptibility make very difficult any epidemiological analysis for estimating hazards specifically due to space radiation exposure. 3) Cytogenetic data undoubtedly revealed that space radiation exposure produce significant damage in cells. However, our knowledge of the basic mechanisms specific to low-dose, to repeated doses and to adaptive response is still poor. The application of new radiobiological techniques, like immunofluorescence, and the use of human tissue models different from blood, like skin fibroblasts, may help in clarifying all the above items

Synthesis and Evaluation of Anticancer Activity of Hyaluronic Acid/Vanillin Conjugates

International audienceNatural phenolic compounds are known not only for their multiplebioactivities but also for their low bioavailability and rapid metabolism in thesystemic circulation. It is well-known that grafting these phenolic compoundsto bio-based polymers such as hyaluronic acid (HA), has the advantage toincrease their stability and water solubility. HA has CD44 receptors that areoverexpressed on cancer cells. This makes from HA an interesting vector forantitumor drug delivery systems. The work reported herein describes thesynthesis and the structural characterization of HA/vanillin conjugates as wellas the size and shape of their aqueous microassemblies using dynamic lightscattering and scattering electron microscopy. Finally, investigation on thebioactivity of such conjugates demonstrates that grafting vanillin to HAimproves significantly its cytotoxicity against MDA-MB231 cancer cells inboth dose and time-dependent manner, and reduces the migration ability aswell as the number and the volume of breast cancer spheres

Impression 3D de composants hyperfréquences pour environnements sévères

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Heat-Resistant 3D Printed Microwave Devices

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Diversity and complexity of ceramide generation after exposure of jurkat leukemia cells to irradiation.

International audiencePURPOSE: To define which intracellular pools of sphingomyelin and ceramide are involved in the triggering of apoptosis of Jurkat leukemia cells in response to gamma-ray exposure. METHODS AND MATERIALS: We examined the kinetics of ceramide generation at the whole-cell level and in different subcellular compartments (plasma membrane rafts, mitochondria, and endoplasmic reticulum) after irradiation with photons. Ceramide was measured by high-performance liquid chromatography or after pulse labeling experiments, and the presence of sphingomyelinase within mitochondria was assessed by electron microscopy. RESULTS: Irradiation of Jurkat leukemia cells resulted in the sequential triggering of sphingomyelin hydrolysis, followed by de novo synthesis that led to a late ceramide response (from 24 h) correlated with the triggering of apoptosis. At the subcellular level, pulse-label experiments, using [(3)H]-palmitate as a precursor, strengthened the involvement of the radiation-induced sphingomyelin breakdown and revealed a very early peak (15 min) of ceramide in plasma membrane rafts. A second peak in mitochondria was measured 4 h after irradiation, resulting from an increase of the sphingomyelin content relating to the targeting of acid sphingomyelinase toward this organelle. CONCLUSION: These data confirm that ceramide is a major determinant in the triggering of radiation-induced apoptosis and highlight the complexity of the sequential compartment-specific ceramide-mediated response of Jurkat leukemia cells to gamma-rays

Activation of Ask1 upstream of the MAPK pathway in irradiated GSH-depleted SQ20B cells.

<p>SQ20B cells were treated with 100 µM DMF and 100 µM BSO for 4 h before irradiation. The drugs were then removed by washing with fresh medium. At different times post irradiation, cells were harvested and the extracted proteins submitted to Western blot analysis. Panel A: levels of phosphorylated Ask1 Panel B: levels of ASK-1 after specific siRNA transfection and downstream phosphorylation of JNK. Panel C: control of apoptosis through the measurement of total caspase activity 72 h after transfection of irradiated GSH-depleted cells with Ask1 SiRNA. Results are expressed as mean ± S.D. for three different experiments. The statistical significance is expressed as <b>***</b>, p<0.001 <i>versus</i> 10 Gy only.</p