Takemura Yukitoshi, Satoh Motohiko, Hatanaka Kenichi, Kubota Shunichiro
a Institute of Industrial Science , The University of Tokyo , Tokyo , Japan.
b Department of Pharmaceutical Sciences , Teikyo Heisei University , Tokyo , Japan.
Biosci Biotechnol Biochem. 2018 Jul;82(7):1159-1164. doi: 10.1080/09168451.2018.1459466. Epub 2018 Apr 24.
Malignant mesothelioma is an asbestos-related aggressive tumor and current therapy remains ineffective. Zebularine as a DNA methyltransferase (DNMT) inhibitor has an anti-tumor effect in several human cancer cells. The aim of the present study was to investigate whether zebularine could induce antiproliferative effect in human malignant mesothelioma cells. Zebularine induced cell growth inhibition in a dose-dependent manner. In addition, zebularine dose-dependently decreased expression of DNMT1 in all malignant mesothelioma cells tested. Cell cycle analysis indicated that zebularine induced S phase delay. Zebularine also induced cell death in malignant mesothelioma cells. In contrast, zebularine did not induce cell growth inhibition and cell death in human normal fibroblast cells. These results suggest that zebularine has a potential for the treatment of malignant mesothelioma by inhibiting cell growth and inducing cell death.
恶性间皮瘤是一种与石棉相关的侵袭性肿瘤，目前的治疗方法仍然无效。泽布替尼作为一种DNA甲基转移酶（DNMT）抑制剂，在几种人类癌细胞中具有抗肿瘤作用。本研究的目的是探讨泽布替尼是否能在人恶性间皮瘤细胞中诱导抗增殖作用。泽布替尼以剂量依赖的方式诱导细胞生长抑制。此外，泽布替尼在所有测试的恶性间皮瘤细胞中剂量依赖性地降低DNMT1的表达。细胞周期分析表明，泽布替尼诱导S期延迟。泽布替尼还诱导恶性间皮瘤细胞死亡。相反，泽布替尼在人正常成纤维细胞中不诱导细胞生长抑制和细胞死亡。这些结果表明，泽布替尼具有通过抑制细胞生长和诱导细胞死亡来治疗恶性间皮瘤的潜力。
