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

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.