Department of Applied Biological Science, Tokyo University of Science, Chiba, Japan.
School of Veterinary Medicine, Azabu University, Kanagawa, Japan.
Biosci Biotechnol Biochem. 2021 Jan 7;85(1):85-91. doi: 10.1093/bbb/zbaa015.
Sulfoglycolipid, SQAP, is a radiosensitizing agent that makes tumor cells more sensitive to radiation therapy. A previous study revealed that SQAP induced the degradation of hypoxia-inducible factor-1α (HIF-1α) and inhibited angiogenesis in a hepatoma model mouse. Herein, we examined the biological activities of SQAP against hepatocarcinoma cells under low oxygen conditions. Cell growth inhibition of SQAP under hypoxic conditions was significantly higher than that under normoxic conditions. In addition, SQAP was found to impair the expression of histone deacetylase (HDAC) under low oxygen conditions. Our present data suggested that SQAP induced the degradation of HIF-1α and then decreased the expression of HDAC1. Unlike known HDAC inhibitors, SQAP increased the acetylation level of histone in cells without inhibition of enzymatic activity of HDACs. Our data demonstrated hypoxia-specific unique properties of SQAP.
硫酸神经鞘氨醇（SQAP）是一种放射增敏剂，可使肿瘤细胞对放射疗法更敏感。先前的一项研究表明，SQAP 可诱导缺氧诱导因子-1α（HIF-1α）降解，并抑制肝癌模型小鼠的血管生成。在此，我们研究了 SQAP 在低氧条件下对肝癌细胞的生物学活性。结果发现，SQAP 在低氧条件下对细胞生长的抑制作用明显高于常氧条件。此外，还发现 SQAP 可在低氧条件下降低组蛋白去乙酰化酶（HDAC）的表达。本研究数据表明，SQAP 诱导 HIF-1α 降解，进而降低 HDAC1 的表达。与已知的 HDAC 抑制剂不同，SQAP 可在不抑制 HDAC 酶活性的情况下增加细胞内组蛋白的乙酰化水平。本研究数据表明，SQAP 具有缺氧特异性的独特性质。
