Department of Applied Biology, CSIR- Indian Institute of Chemical Technology, Hyderabad, 500007, Telangana, India.
Academy of Scientific and Innovative Research, Ghaziabad, 201002, Uttar Pradesh, India.
Mol Biol Rep. 2021 May;48(5):4973-4979. doi: 10.1007/s11033-021-06481-z. Epub 2021 Jun 14.
Neuroblastoma (NB) is the most common childhood cancer that arises from the sympathetic nervous system. NB is characterized by poor prognosis. One of the strategies to control NB is activating the differentiation process in undifferentiated NB cells. Many differentiating agents including 13-cis-retinoic acid (RA) led to disappointing results. In the current study, we investigated the effect of Quisinostat/JNJ-26481585(JNJ) on NB SK-N-SH cells differentiation. The SK-N-SH cell differentiation was observed by morphology and neurite length measurement. The cell cycle arrest was determined by FACS analysis. The relative levels of autophagy marker LC3-II, neuronal markers βIII-tubulin and Eno-2, cell cycle related proteins cyclin D1 and CDK 4 were detected by western blotting. JNJ induces differentiation in SK-N-SH cells, as evident by the morphological features and expression of neuronal markers, βIII-tubulin and Eno-2. Cell cycle arrest at G1 phase was confirmed by a decrease in the expression of cyclin D1 and CDK 4. Furthermore, we also observed that autophagy plays an important role in JNJ induced cell differentiation of SK-N-SH cells. We demonstrated that autophagy is induced upon JNJ treatment and is important for the neuronal differentiation of human SK-N-SH cells.
神经母细胞瘤(NB)是最常见的起源于交感神经系统的儿童癌症。NB 的预后较差。控制 NB 的策略之一是在未分化的 NB 细胞中激活分化过程。许多分化剂,包括 13-顺式视黄酸(RA),导致了令人失望的结果。在本研究中,我们研究了 Quisinostat/JNJ-26481585(JNJ)对 NB SK-N-SH 细胞分化的影响。通过形态学和神经突长度测量观察 SK-N-SH 细胞分化。通过 FACS 分析确定细胞周期停滞。通过 Western blot 检测自噬标记物 LC3-II、神经元标志物 βIII-微管蛋白和 Eno-2、细胞周期相关蛋白 cyclin D1 和 CDK 4 的相对水平。JNJ 诱导 SK-N-SH 细胞分化,表现为形态特征和神经元标志物 βIII-微管蛋白和 Eno-2 的表达。细胞周期停滞在 G1 期被 cyclin D1 和 CDK 4 的表达减少所证实。此外,我们还观察到自噬在 JNJ 诱导的 SK-N-SH 细胞分化中起重要作用。我们证明 JNJ 处理后自噬被诱导,并且对于人 SK-N-SH 细胞的神经元分化很重要。