期刊
CELLS
卷 11, 期 23, 页码 -出版社
MDPI
DOI: 10.3390/cells11233780
关键词
radioresistant cells; hyaluronan; oral squamous cell carcinoma; 4-methylumbelliferone; hyaluronan synthase 3; oxidative stress; superoxide dismutase; intracellular hyaluronan; radiosensitization
类别
资金
- JST SPRING
- [JPMJSP2152]
4-MU enhances radiosensitization of radioresistant cells by increasing intracellular oxidative stress and suppressing cancer stem cell-like phenotype. These results may be associated with HAS3 or intracellular HA synthesized by HAS3.
Radioresistant (RR) cells are poor prognostic factors for tumor recurrence and metastasis after radiotherapy. The hyaluronan (HA) synthesis inhibitor, 4-methylumbelliferone (4-MU), shows anti-tumor and anti-metastatic effects through suppressing HA synthase (HAS) expression in various cancer cells. We previously reported that the administration of 4-MU with X-ray irradiation enhanced radiosensitization. However, an effective sensitizer for radioresistant (RR) cells is yet to be established, and it is unknown whether 4-MU exerts radiosensitizing effects on RR cells. We investigated the radiosensitizing effects of 4-MU in RR cell models. This study revealed that 4-MU enhanced intracellular oxidative stress and suppressed the expression of cluster-of-differentiation (CD)-44 and cancer stem cell (CSC)-like phenotypes. Interestingly, eliminating extracellular HA using HA-degrading enzymes did not cause radiosensitization, whereas HAS3 knockdown using siRNA showed similar effects as 4-MU treatment. These results suggest that 4-MU treatment enhances radiosensitization of RR cells through enhancing oxidative stress and suppressing the CSC-like phenotype. Furthermore, the radiosensitizing mechanisms of 4-MU may involve HAS3 or intracellular HA synthesized by HAS3.
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