scholarly journals Lipid droplets and ferritin heavy chain: a devilish liaison in human cancer cell radioresistance

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Luca Tirinato ◽  
Maria Grazia Marafioti ◽  
Francesca Pagliari ◽  
Jeannette Jansen ◽  
Ilenia Aversa ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Heavy Chain ◽  
Lipid Droplets ◽  
Molecular Mechanisms ◽  
Human Cancer ◽  
X Ray ◽  
Ferritin Heavy Chain ◽  
Clonogenic Potential ◽  
Radiation Treatments ◽  
Made In

Although much progress has been made in cancer treatment, the molecular mechanisms underlying cancer radioresistance (RR) as well as the biological signatures of radioresistant cancer cells still need to be clarified. In this regard, we discovered that breast, bladder, lung, neuroglioma and prostate 6 Gy X-ray resistant cancer cells were characterized by an increase of Lipid Droplet (LD) number and that the cells containing highest LDs showed the highest clonogenic potential after irradiation. Moreover, we observed that LD content was tightly connected with the iron metabolism and in particular with the presence of the ferritin heavy chain (FTH1). In fact, breast and lung cancer cells silenced for the FTH1 gene showed a reduction in the LD numbers and, by consequence, became radiosensitive. FTH1 overexpression as well as iron-chelating treatment by Deferoxamine were able to restore the LD amount and RR. Overall, these results provide evidence of a novel mechanism behind RR in which LDs and FTH1 are tightly connected to each other, a synergistic effect which might be worth deeply investigating in order to make cancer cells more radiosensitive and improve the efficacy of radiation treatments.

scholarly journals Lipid Droplets and Ferritin Heavy Chain: a Devilish Liaison in Cancer Radioresistance

2021 ◽  
Author(s):  
Luca Tirinato ◽  
Maria Grazia Marafioti ◽  
Francesca Pagliari ◽  
Jeanette Jansen ◽  
Ilenia Aversa ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Heavy Chain ◽  
Lipid Droplets ◽  
Molecular Mechanisms ◽  
X Ray ◽  
Ferritin Heavy Chain ◽  
Clonogenic Potential ◽  
Radiation Treatments ◽  
Made In

Although much progress has been made in cancer treatment, the molecular mechanisms underlying cancer radioresistance (RR) as well as the biological characteristic of radioresistant cancer cells still need to be clarified. In this regard, we discovered that breast, bladder, lung, neuroglioma and prostate 6 Gy X-ray resistant cells were characterized by an increase of Lipid Droplet (LD) number and that the cells containing highest LDs showed the highest clonogenic potential after irradiation. Moreover, we observed that LD content was tightly connected with the iron metabolism and in particular with the presence of the ferritin heavy chain (FTH1). In fact, breast and lung cancer cells silenced for the FTH1 gene showed a reduction in the LD numbers and, by consequence, became radiosensitive. FTH1 restoration as well as iron-chelating treatment by Deferoxamine were able to restore the LD amount and RR. Overall, these results provide evidence of a novel molecular mechanism behind RR in which LDs and FTH1 are tightly connected to each other, a synergistic effect which might be worth deeply investigating in order to make cancer cells more radiosensitive and improve the efficacy of radiation treatments.

scholarly journals PER2 Circadian Oscillation Sensitizes Esophageal Cancer Cells to Chemotherapy

Biology ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 266
Author(s):  
Juan Alfonso Redondo ◽  
Romain Bibes ◽  
Alizée Vercauteren Drubbel ◽  
Benjamin Dassy ◽  
Xavier Bisteau ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Circadian Rhythm ◽  
Survival Rate ◽  
Circadian Clock ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Human Cancer ◽  
Response To Therapy ◽  
Circadian Oscillation ◽  
Resistance To Therapy

Esophageal squamous cell carcinoma (eSCC) accounts for more than 85% cases of esophageal cancer worldwide and the 5-year survival rate associated with metastatic eSCC is poor. This low survival rate is the consequence of a complex mechanism of resistance to therapy and tumor relapse. To effectively reduce the mortality rate of this disease, we need to better understand the molecular mechanisms underlying the development of resistance to therapy and translate that knowledge into novel approaches for cancer treatment. The circadian clock orchestrates several physiological processes through the establishment and synchronization of circadian rhythms. Since cancer cells need to fuel rapid proliferation and increased metabolic demands, the escape from circadian rhythm is relevant in tumorigenesis. Although clock related genes may be globally repressed in human eSCC samples, PER2 expression still oscillates in some human eSCC cell lines. However, the consequences of this circadian rhythm are still unclear. In the present study, we confirm that PER2 oscillations still occur in human cancer cells in vitro in spite of a deregulated circadian clock gene expression. Profiling of eSCC cells by RNAseq reveals that when PER2 expression is low, several transcripts related to apoptosis are upregulated. Consistently, treating eSCC cells with cisplatin when PER2 expression is low enhances DNA damage and leads to a higher apoptosis rate. Interestingly, this process is conserved in a mouse model of chemically-induced eSCC ex vivo. These results therefore suggest that response to therapy might be enhanced in esophageal cancers using chronotherapy.

scholarly journals Selective Enhancing Effect of Early Mitotic Inhibitor 1 (Emi1) Depletion on the Sensitivity of Doxorubicin or X-ray Treatment in Human Cancer Cells

2013 ◽  
Vol 288 (24) ◽  
pp. 17238-17252 ◽  
Author(s):  
Natsumi Shimizu ◽  
Nakako Izumi Nakajima ◽  
Takaaki Tsunematsu ◽  
Ikuko Ogawa ◽  
Hidehiko Kawai ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Human Cancer ◽  
Enhancing Effect ◽  
X Ray ◽  
Human Cancer Cells ◽  
Mitotic Inhibitor

Molecular mechanisms of G0/G1 cell-cycle arrest and apoptosis induced by terfenadine in human cancer cells

2003 ◽  
Vol 37 (1) ◽  
pp. 39-50 ◽  
Author(s):  
Jean-Dean Liu ◽  
Ying-Jan Wang ◽  
Chien-Ho Chen ◽  
Cheng-Fei Yu ◽  
Li-Ching Chen ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Human Cancer ◽  
Human Cancer Cells ◽  
Cycle Arrest ◽  
G1 Cell Cycle Arrest

scholarly journals A Morphological and Histological Investigation of Imperfect Lungfish Fin Regeneration

2021 ◽  
Vol 9 ◽  
Author(s):  
Vivien Bothe ◽  
Igor Schneider ◽  
Nadia B. Fröbisch
Keyword(s):  
Tissue Regeneration ◽  
Molecular Mechanisms ◽  
Limb Regeneration ◽  
Body Parts ◽  
Serial Sections ◽  
Fin Regeneration ◽  
X Ray ◽  
The Past ◽  
Great Progress ◽  
Made In

Regeneration, the replacement of body parts in a living animal, has excited scientists for centuries and our knowledge of vertebrate appendage regeneration has increased significantly over the past decades. While the ability of amniotes to regenerate body parts is very limited, members of other vertebrate clades have been shown to have rather high regenerative capacities. Among tetrapods (four-limbed vertebrates), only salamanders show unparalleled capacities of epimorphic tissue regeneration including replacement of organ and body parts in an apparently perfect fashion. The closest living relatives of Tetrapoda, the lungfish, show regenerative abilities that are comparable to those of salamanders and recent studies suggest that these high regenerative capacities may indeed be ancestral for bony fish (osteichthyans) including tetrapods. While great progress has been made in recent years in understanding the cellular and molecular mechanisms deployed during appendage regeneration, comparatively few studies have investigated gross morphological and histological features of regenerated fins and limbs. Likewise, rather little is known about how fin regeneration compares morphologically to salamander limb regeneration. In this study, we investigated the morphology and histology of regenerated fins in all three modern lungfish families. Data from histological serial sections, 3D reconstructions, and x-ray microtomography scans were analyzed to assess morphological features, quality and pathologies in lungfish fin regenerates. We found several anomalies resulting from imperfect regeneration in regenerated fins in all investigated lungfish species, including fusion of skeletal elements, additional or fewer elements, and distal branching. The similarity of patterns in regeneration abnormalities compared to salamander limb regeneration lends further support to the hypothesis that high regenerative capacities are plesiomorphic for sarcopterygians.

scholarly journals RuvBL1 Maintains Resistance to TRAIL-Induced Apoptosis by Suppressing c-Jun/AP-1 Activity in Non-Small Cell Lung Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Hao Li ◽  
Taoran Zhou ◽  
Yue Zhang ◽  
Hengyi Jiang ◽  
Jing Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Therapeutic Strategy ◽  
Molecular Mechanisms ◽  
Human Cancer ◽  
Human Cancer Cells ◽  
The Common ◽  
Trail Resistance ◽  
Induced Apoptosis ◽  
Necrosis Factor

Lung cancer is the common malignant tumor with the highest death rate in the world. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) as a potential anticancer agent induces selective apoptotic death of human cancer cells. Unfortunately, approximately half of lung cancer cell lines are intrinsically resistant to TRAIL-induced cell death. In this study, we identified RuvBL1 as a repressor of c-Jun/AP-1 activity, contributing to TRAIL resistance in lung cancer cells. Knocking down RuvBL1 effectively sensitized resistant cells to TRAIL, and overexpression of RuvBL1 inhibited TRAIL-induced apoptosis. Moreover, there was a negative correlation expression between RuvBL1 and c-Jun in lung adenocarcinoma by Oncomine analyses. High expression of RuvBL1 inversely with low c-Jun in lung cancer was associated with a poor overall prognosis. Taken together, our studies broaden the molecular mechanisms of TRAIL resistance and suggest the application of silencing RuvBL1 synergized with TRAIL to be a novel therapeutic strategy in lung cancer treatment.

X–Ray Diffraction (XRD), Powder X–Ray Diffraction (PXRD) and Energy–Dispersive X–Ray Diffraction (EDXRD) Comparative Study on Malignant and Benign Human Cancer Cells and Tissues under Synchrotron Radiation

2018 ◽  
Vol 1 (1) ◽  
pp. 1-14 ◽  
Keyword(s):  
Synchrotron Radiation ◽  
Comparative Study ◽  
Cancer Cells ◽  
Human Cancer ◽  
Energy Dispersive ◽  
X Ray Diffraction ◽  
X Ray ◽  
Human Cancer Cells ◽  
Before And After

In the current study, we have experimentally and comparatively investigated and compared malignant human cancer cells and tissues before and after irradiating of synchrotron radiation using X–Ray Diffraction (XRD), Powder X–Ray Diffraction (PXRD) and Energy–Dispersive X– Ray Diffraction (EDXRD).

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