Selenomethionine suppresses head and neck squamous cell carcinoma progression through TopBP1/ATR and TCAB1 signaling

Histol Histopathol. 2024 Jul;39(7):877-887. doi: 10.14670/HH-18-665. Epub 2023 Sep 11.

Abstract

Objective: Head and neck squamous cell carcinoma (HNSCC) is a histological type of cancer originating from the head and neck. Selenium complexes have been considered as a potential treatment for HNSCC. Therefore, the present work focused on probing the mechanism of L-selenomethionine (SeMet) in HNSCC treatment.

Methods: MTT and colony formation assays were carried out to analyze the survival rate and proliferation of HNSCC cells, respectively. TUNEL staining was performed to examine apoptosis of HNSCC cells. Additionally, qRT-PCR and Western blotting assays were performed to measure mRNA and protein levels, separately.

Results: SeMet treatment significantly hindered the survival and promoted the apoptosis of HNSCC cells in a dose- and time-dependently. SeMet administration promoted expression of TopBP1, ATR, H2AX, p-ATR and γ-H2AX, and suppressed that of TCAB1. Importantly, SeMet treatment suppressed the proliferation and facilitated the apoptosis of HNSCC cells, which were partly reversed by down-regulation of TopBP1 or up-regulation of TCAB1. The activation of SeMet to TopBP1/ATR signaling was rescued by TCAB1 up-regulating, and the inhibition of SeMet to TCAB1 expression was rescued by TopBP1 silencing.

Conclusion: Our findings show that SeMet inhibits the proliferation of HNSCC cells and promotes their apoptosis by targeting TopBP1/ATR and TCAB1 signaling. SeMet is a potential method for HNSCC treatment.

MeSH terms

  • Apoptosis* / drug effects
  • Ataxia Telangiectasia Mutated Proteins / metabolism
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Disease Progression
  • Gene Expression Regulation, Neoplastic / drug effects
  • Head and Neck Neoplasms* / drug therapy
  • Head and Neck Neoplasms* / pathology
  • Humans
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Selenium-Binding Proteins / genetics
  • Selenium-Binding Proteins / metabolism
  • Selenomethionine* / pharmacology
  • Signal Transduction* / drug effects
  • Squamous Cell Carcinoma of Head and Neck* / drug therapy
  • Squamous Cell Carcinoma of Head and Neck* / pathology

Substances

  • Ataxia Telangiectasia Mutated Proteins
  • ATR protein, human
  • Carrier Proteins
  • DNA-Binding Proteins
  • Nuclear Proteins
  • SELENBP1 protein, human
  • Selenium-Binding Proteins
  • Selenomethionine