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BMC Oral Health

BMC Oral Health

IF: 2.6
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Effect and mechanism of resveratrol on ferroptosis mediated by p53/SLC7A11 in oral squamous cell carcinoma.

Published:10 July 2024 DOI: 10.1186/s12903-024-04395-3 PMID: 38987730
Chen Mao,?Liqiang Gong,?Wenming Kang

Abstract

Objective: Resveratrol (Res) is a natural phytoestrogen with antitumor activity. This study sought to investigate the role of Res in ferroptosis in oral squamous cell carcinoma (OSCC).

Methods: Normal human oral keratinocyte (HOK)/oral OSCC (CAL-27/SCC-9) cell lines were treated with different doses of Res. Res toxicity was determined by MTT assay, with half maximal inhibitory concentration values of Res on CAL-27 and SCC-9 cells calculated. Cell viability/colony formation efficiency/migration/invasion/cycle were assessed by CCK-8/colony formation assay/transwell assay/flow cytometry. The expression of p53 protein in the nucleus and cytoplasm, glutathione peroxidase 4 (GPX4) expression, and SLC7A11 messenger RNA (mRNA) and protein expression levels were determined by Western blot and RT-qPCR. Fe2+ content, reactive oxygen species (ROS) level, reduced glutathione (GSH), and lactate dehydrogenase (LDH) release were assessed.

Results: Medium- to low-dose Res had no toxic effect on HOK cells, while high-dose Res markedly reduced HOK cell viability. Res significantly suppressed the viability of OSCC cells (CAL-27 and SCC-9). Res inhibited OSCC cell colony formation/migration/invasion, and induced G1 phase arrest. Res caused the translocation of p53 protein to the nucleus, obviously increased Fe2+ content, ROS level and LDH release, decreased GSH content and GPX4 protein expression, and induced ferroptosis. Down-regulation of p53 partially reversed the inhibitory effects of Res on CAL-27 cell malignant behaviors. Res inhibited SLC7A11 transcription by promoting p53 entry into the nucleus. SLC7A11 overexpression negated the the regulatory effects of p53 knockout on the role of Res in OSCC cell malignant behaviors and ferroptosis.

Conclusion: Res accelerated ferroptosis and inhibited malignant behaviors in OSCC cells by regulating p53/SLC7A11.

Substances (4)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Pifithrin-α, p-nitro, cyclic 60477-38-5 C15H13N3O2S 75 suppliers $37.00-$817.00
Pifithrin-α, p-nitro, cyclic 60477-38-5 C15H13N3O2S 75 suppliers $37.00-$817.00
Pifithrin-α, p-nitro, cyclic 60477-38-5 C15H13N3O2S 75 suppliers $37.00-$817.00
Pifithrin-α, p-nitro, cyclic 60477-38-5 C15H13N3O2S 75 suppliers $37.00-$817.00

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