scholarly journals Methylseleninic Acid Induces Lipid Peroxidation and Radiation Sensitivity in Head and Neck Cancer Cells

2019 ◽  
Vol 20 (1) ◽  
pp. 225 ◽  
Author(s):  
John T. Lafin ◽  
Ehab H. Sarsour ◽  
Amanda L. Kalen ◽  
Brett A. Wagner ◽  
Garry R. Buettner ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Head And Neck ◽  
Cancer Cells ◽  
Clonogenic Assay ◽  
Radiation Sensitivity ◽  
Selenium Compounds ◽  
Ferric Thiocyanate ◽  
Methylseleninic Acid ◽  
Intracellular Glutathione ◽  
A Cell

Combination radiation and chemotherapy are commonly used to treat locoregionally advanced head and neck squamous cell carcinoma (HNSCC). Aggressive dosing of these therapies is significantly hampered by side effects due to normal tissue toxicity. Selenium represents an adjuvant that selectively sensitizes cancer cells to these treatments modalities, potentially by inducing lipid peroxidation (LPO). This study investigated whether one such selenium compound, methylseleninic acid (MSA), induces LPO and radiation sensitivity in HNSCC cells. Results from 4,4-difluoro-4-bora-3a,4a-diaza-S-indacene (BODIPY) C11 oxidation and ferric thiocyanate assays revealed that MSA induced LPO in cells rapidly and persistently. Propidium iodide (PI) exclusion assay found that MSA was more toxic to cancer cells than other related selenium compounds; this toxicity was abrogated by treatment with α-tocopherol, an LPO inhibitor. MSA exhibited no toxicity to normal fibroblasts at similar doses. MSA also sensitized HNSCC cells to radiation as determined by clonogenic assay. Intracellular glutathione in cancer cells was depleted following MSA treatment, and supplementation of the intracellular glutathione pool with N-acetylcysteine sensitized cells to MSA. The addition of MSA to a cell-free solution of glutathione resulted in an increase in oxygen consumption, which was abrogated by catalase, suggesting the formation of H2O2. Results from this study identify MSA as an inducer of LPO, and reveal its capability to sensitize HNSCC to radiation. MSA may represent a potent adjuvant to radiation therapy in HNSCC.

scholarly journals Protein-partners of selenoprotein SELM and the role of selenium compounds in regulation of its expression in human cancer cells

2019 ◽  
Vol 488 (2) ◽  
pp. 212-216
Author(s):  
E. G. Varlamova ◽  
M. V. Goltyaev ◽  
E. E. Fesenko
Keyword(s):  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Sodium Selenite ◽  
Cancer Cell Lines ◽  
Breast Adenocarcinoma ◽  
Selenium Compounds ◽  
Cytoplasmic Actin ◽  
Methylseleninic Acid ◽  
Fibrosarcoma Cells

The search of potential partners of human SELM in lysates of two cancer cell lines HT-1080 (fibrosarcoma) and MCF-7 (breast adenocarcinoma) was carried out. Two cytoplasmic actin isoforms: cytoplasmic actin 1 (cytoskeleton b-actin) and cytoplasmic actin 2 (cytoskeletal g-actin) was identified as partners. In addition, the influence of two widely used antitumor selenium compounds (sodium selenite and methylseleninic acid) on the expression SELM in cancer cells was studied. According to the results obtained by real-time PCR and Western blotting, we was concluded that 1 µM and 10 µM sodium selenite was not affected on the expression SELM in fibrosarcoma cells, whereas in breast adenocarcinoma cells 1 µM sodium selenite slightly increased of expression and 10 µM resulted in a significant decrease (about 2 times). Methylseleninic acid in both cancer cell lines increased the expression of SELM gene, the most pronounced effect was observed when fibrosarcoma cells were treated with 10 µM MSC (increased expression of the hSelm gene by almost 4 times).

scholarly journals 7-Dehydrocholesterol is an endogenous suppressor of ferroptosis

2021 ◽  
Author(s):  
Jose Pedro Friedmann Angeli ◽  
Florencio Porto Freitas ◽  
Palina Nepachalovich ◽  
Lohans Puentes ◽  
Omkar Zilka ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Cell Death ◽  
Cancer Cells ◽  
Survival Function ◽  
Peroxyl Radicals ◽  
Metabolic Adaptation ◽  
Compelling Evidence ◽  
Intrinsic Mechanism ◽  
A Cell ◽  
Developing Neurons

Abstract Ferroptosis is a form of cell death that has received considerable attention not only as a means to eradicate defined tumour entities but also because it provides unforeseen insights into the metabolic adaptation exploited by tumours to counteract phospholipid oxidation. Here, we identify a pro-ferroptotic activity of 7-dehydrocholesterol reductase (DHCR7) and an unexpected pro-survival function of its substrate, 7-dehydrocholesterol (7-DHC). Although previous studies suggested that high levels of 7-DHC are cytotoxic to developing neurons and favour lipid peroxidation, we now demonstrate that 7-DHC accumulation confers a robust pro-survival function in cancer cells. 7-DHC, due to its far superior reactivity towards peroxyl radicals, is shown here to effectively shield (phospho)lipids from autoxidation and subsequent fragmentation. We further demonstrate in a subset of ferroptosis-sensitive Burkitt lymphomas - where DHCR7 mutations have been reported - that the accumulation of 7-DHC is sufficient to suppress the basal sensitivity of cells toward ferroptosis, thereby translating into an unexpected growth advantage. Conclusively, our findings provide compelling evidence of a yet-unrecognised anti-ferroptotic activity of 7-DHC as a cell-intrinsic mechanism that could be exploited by cancer cells to escape ferroptosis.

scholarly journals Roles of microRNAs in Regulating Cancer Stemness in Head and Neck Cancers

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1742
Author(s):  
Melysa Fitriana ◽  
Wei-Lun Hwang ◽  
Pak-Yue Chan ◽  
Tai-Yuan Hsueh ◽  
Tsai-Tsen Liao
Keyword(s):  
Growth Factor ◽  
Head And Neck ◽  
Cancer Cells ◽  
Signaling Pathways ◽  
Epithelial To Mesenchymal Transition ◽  
Survival Rates ◽  
Growth Factor Receptor ◽  
Cancer Stemness ◽  
Mesenchymal Transition

Head and neck squamous cell carcinomas (HNSCCs) are epithelial malignancies with 5-year overall survival rates of approximately 40–50%. Emerging evidence indicates that a small population of cells in HNSCC patients, named cancer stem cells (CSCs), play vital roles in the processes of tumor initiation, progression, metastasis, immune evasion, chemo-/radioresistance, and recurrence. The acquisition of stem-like properties of cancer cells further provides cellular plasticity for stress adaptation and contributes to therapeutic resistance, resulting in a worse clinical outcome. Thus, targeting cancer stemness is fundamental for cancer treatment. MicroRNAs (miRNAs) are known to regulate stem cell features in the development and tissue regeneration through a miRNA–target interactive network. In HNSCCs, miRNAs act as tumor suppressors and/or oncogenes to modulate cancer stemness and therapeutic efficacy by regulating the CSC-specific tumor microenvironment (TME) and signaling pathways, such as epithelial-to-mesenchymal transition (EMT), Wnt/β-catenin signaling, and epidermal growth factor receptor (EGFR) or insulin-like growth factor 1 receptor (IGF1R) signaling pathways. Owing to a deeper understanding of disease-relevant miRNAs and advances in in vivo delivery systems, the administration of miRNA-based therapeutics is feasible and safe in humans, with encouraging efficacy results in early-phase clinical trials. In this review, we summarize the present findings to better understand the mechanical actions of miRNAs in maintaining CSCs and acquiring the stem-like features of cancer cells during HNSCC pathogenesis.

scholarly journals Ionizing radiation affects the composition of the proteome of extracellular vesicles released by head-and-neck cancer cells in vitro

2019 ◽  
Vol 60 (3) ◽  
pp. 289-297 ◽  
Author(s):  
Agata Abramowicz ◽  
Anna Wojakowska ◽  
Lukasz Marczak ◽  
Malgorzata Lysek-Gladysinska ◽  
Mateusz Smolarz ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Ionizing Radiation ◽  
Head And Neck ◽  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Neck Cancer
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