Ascorbic acid induces ferroptosis via STAT3/GPX4 signaling in oropharyngeal cancer.

Ferroptosis is recognized as a new type of regulated cell death initiated by iron-dependent accumulation of lipid peroxidation. Recent studies have shown that the administration of ascorbic acid (AA) preferentially kills tumor cells by impairing iron metabolism and exerting pro-oxidant effects. Despite mounting evidence indicating the anticancer potential of AA, the underlying molecular mechanisms remain unknown. In this study, we demonstrated that AA decreased cell viability and Ki67 expression, along with its accumulation in the G0/G1 phase in FaDu and SCC-154 cell lines. Furthermore, AA exposure induced morphological changes in mitochondria associated with ferroptosis. AA-induced ferroptosis is accompanied by depletion of glutathione (GSH) and increased levels of ferrous ions (Fe2+), reactive oxygen species (ROS), and malondialdehyde (MDA). However, these ferroptotic effects were ameliorated by deferoxamine and N-acetylcysteine. Network pharmacology results showed that signal transducer and activator of transcription 3 (STAT3) is a key target of AA against oropharyngeal cancer. AA markedly downregulates the relative mRNA expression of STAT3 and glutathione peroxidase 4 (GPX4). Immunoblotting indicated that the protein levels of p-STAT3, STAT3, and GPX4 in FaDu and SCC-154 cells decreased significantly in response to AA treatment. Mechanistically, a chromatin immunoprecipitation assay confirmed that AA exposure reduced STAT3 expression in the GPX4 promoter region. Additionally, AA-induced inhibition of cell growth and ferroptosis was suppressed by STAT3 and GPX4 overexpression, respectively. In summary, AA inhibited oropharyngeal cancer cell growth in vitro by regulating STAT3/GPX4-mediated ferroptosis, which may provide a novel theoretical basis for the clinical treatment of oropharyngeal cancer with AA.

Ascorbic acid acts as an anticancer agent by inducing ferroptosis, reducing the viability of SCC-154 and FaDu cells.Ascorbic acid-mediated ferroptosis acts through STAT3/GPX4 pathway.The induction of ferroptosis has a significant potential for cancer therapy.

Modified Gugging Swallowing Screen: A New Bedside Evaluation Tool for Swallowing Function in Patients with Open Partial Laryngectomy before Oral Feeding: A Single-Centre Retrospective Study.

BACKGROUND: Dysphagia is a prevalent complication following partial laryngectomy. We aimed to introduce a novel bedside evaluation tool, the modified Gugging Swallowing Screen (GUSS), and evaluate its reliability and validity in patients with open partial laryngectomy before oral feeding. METHODS: We conducted a retrospective analysis of 120 patients with laryngeal cancer, including 40 hospitalized patients who underwent open partial laryngectomy. On the same day before oral feeding, we performed the modified GUSS, videofluoroscopic swallowing study (VFSS), and fiberoptic endoscopic evaluation of swallowing (FEES) to evaluate swallowing function. Two independent trained nurses assessed all patients for interrater reliability of modified GUSS. We compared the results of the modified GUSS with VFSS for predictive validity, and VFSS results for solid, semisolid, and liquid intake for content validity. RESULTS: The results of VFSS and FEES showed a strong correlation and consistency (rs = 0.952, p < 0.01; κ = 0.800 to 1.000, p < 0.01). The modified GUSS exhibited substantial to excellent interrater reliability across all classification categories (rs = 0.961, p < 0.01; κ = 0.600 to 1.000, p < 0.01) and demonstrated excellent consistency and predictive validity compared to VFSS (rs = -0.931, p < 0.01; κ = 0.800 to 1.000, p < 0.01). Content validity revealed that the risk of aspiration during solid intake was lower than that during semisolid intake (p < 0.01), and the risk of aspiration during semisolid intake was lower than that during liquid intake (p < 0.01), therefore confirming the subtest sequence of the modified GUSS. CONCLUSIONS: We successfully modified GUSS for patients with open partial laryngectomy. Moreover, the new bedside screening tool was validated as an effective tool for evaluating swallowing function and the risk of aspiration in patients with open partial laryngectomy before oral feeding.