erastin and Squamous-Cell-Carcinoma-of-Head-and-Neck

Unfavorable clinical outcomes mean that cancer researchers must attempt to develop novel therapeutic strategies to overcome therapeutic resistance in patients with HNSCC. Recently, ferroptosis was shown to be a promising pathway possessing druggable targets, such as xCT (SLC7A11). Unfortunately, little is known about the molecular mechanisms underlying the susceptibility of HNSCC cells to ferroptosis. The goal of this study was to determine whether HNSCC cells with activated Erk1/2 are vulnerable to ferroptosis induction. Our results have shown that xCT (SLC7A11) was overexpressed in malignant tissues obtained from the patients with HNSCC, whereas normal mucosa demonstrated weak expression of the protein. In order to investigate the role of Erk1/2 in the decrease in cell viability caused by erastin, xCT-overexpressing FaDu and SCC25 HNSCC cells were used. The ravoxertinib-dependent inhibition of Erk1/2 signaling led to the decrease in erastin efficacy due to the effect on ROS production and the upregulation of ROS scavengers SOD1 and SOD2, resulting in repressed lipid peroxidation. Therefore, it was concluded that the erastin-dependent activation of ferroptosis seems to be a promising approach which can be further developed as an additional strategy for the treatment of HNSCC. As ferroptosis induction via erastin is strongly dependent on the expression of Erk1/2, this MAP kinase can be considered as a predictor for cancer cells' response to erastin.

Topics: Ferroptosis; Head and Neck Neoplasms; Humans; Reactive Oxygen Species; Squamous Cell Carcinoma of Head and Neck

Oral squamous cell carcinomas are one of the most common cancers worldwide with aggressive behavior and poor prognosis. Reactive oxygen species (ROS) are associated with cancer and cause various types of regulated cell death (RCD). Inducing the RCD pathway by modulating ROS levels is imperative to conquer cancers. The aim of this study is to investigate the synergistic anticancer effects of melatonin and erastin on ROS modulation and subsequent RCD induction.. Human tongue squamous cell carcinoma cell lines (SCC-15 cells) were treated with melatonin, erastin, or their combination. Cell viability, ROS levels, autophagy, apoptosis, and ferroptosis levels were tested according to the results of the PCR array, which were verified with/without the induction and inhibition of ROS by H. ROS levels were increased by the administration of melatonin at high concentrations (mM), and the combination of melatonin with erastin enhanced the levels of malonic dialdehyde, ROS, and lipid ROS, and reduced the levels of glutamate and glutathione. SQSTM1/p62, LC3A/B, cleaved caspase-3, and PARP1 protein levels in SCC-15 cells were also increased by melatonin plus erastin treatment, which further increased as ROS accumulated, and decreased as ROS levels were suppressed. Combined treatment of melatonin and erastin markedly reduced the tumor size in vivo, demonstrated no obvious systemic side effects, and significantly enhanced the apoptosis and ferroptosis levels in the tumor tissues, in parallel with decreased autophagy levels.. Melatonin combined with erastin exhibits synergistic anticancer effects without adverse reactions. Herein, this combination might become a promising alternative strategy for oral cancer treatment.

Topics: Animals; Apoptosis; Autophagy; Carcinoma, Squamous Cell; Disease Models, Animal; Ferroptosis; Head and Neck Neoplasms; Humans; Hydrogen Peroxide; Melatonin; Mice; Mouth Neoplasms; Reactive Oxygen Species; Squamous Cell Carcinoma of Head and Neck; Tongue Neoplasms

MiRNA is a small molecule RNA that plays an important role in a variety of physiological and pathological processes., and miR-34c-3p has been demonstrated to be closely related to the occurrence of tumors. Ferroptosis is a new form of cell death characterized by lipid-based reactive oxygen species accumulation. However, it is still unclear how miR-34c-3p influences the development of oral squamous cell carcinoma (OSCC) by regulating ferroptosis. Therefore, the main objective of this study was to explore the role and mechanism of miR-34c-3p in OSCC.. The expression of miR-34c-3p in OSCC and matched normal tissues was detected by quantitative real-time PCR (qRT-PCR). Subsequently, the effect of miR-34c-3p overexpression on cell proliferation and ferroptosis was evaluated using CCK8, colony formation assays, Live/Dead staining, Western blotting analysis, ROS, MDA, and GSH assay.. The results showed lower expression of miR-34c-3p in OSSC compared with normal tissues. Overexpression of miR-34c-3p in SCC-25 cells suppressed cell proliferation. In addition, the overexpression of miR-34c-3p promoted ferroptosis by increasing ROS, MDA, and iron and decreasing GSH and GPX4 levels in SCC-25 cells.. Our findings revealed a novel strategy to upregulate erastin-induced ferroptosis in OSCC through the miR-34c-3p/SLC7A11 axis, suggesting new insights into OSCC and a potentially useful therapeutic strategy for OSCC.

Topics: Aged; Amino Acid Transport System y+; Cell Proliferation; Female; Ferroptosis; Humans; Male; MicroRNAs; Middle Aged; Piperazines; Squamous Cell Carcinoma of Head and Neck; Up-Regulation

Ferroptosis, a regulated form of cell necrosis was previously reported to be induced upon pharmacological targeting of the cystine transporter SLC7A11 in Head and neck Squamous Cell Carcinoma (HNSCC). Whether tumors arising in a context of chronic infection with Human Papillomavirus (HPV) are sensitive to ferroptosis is unknown. Using RNAseq data (both whole-tumor and single-cell sequencing) we report that HPV positive (HPV

Topics: Acetylcysteine; Amino Acid Transport System y+; Biological Transport, Active; Biomarkers; Cell Line, Tumor; Cystine; Ferroptosis; Gene Expression Regulation, Neoplastic; Glutathione; Head and Neck Neoplasms; Human papillomavirus 16; Humans; Oncogene Proteins, Viral; Papillomavirus E7 Proteins; Papillomavirus Infections; Phospholipid Hydroperoxide Glutathione Peroxidase; Piperazines; Repressor Proteins; RNA-Seq; Single-Cell Analysis; Squamous Cell Carcinoma of Head and Neck