Kim Min Young, Park Seong-Joon, Shim Jae Woong, Yang Kwangmo, Kang Ho Sung, Heo Kyu
Research Center, Dongnam Institute of Radiological and Medical Science (DIRAMS), Busan 619-953, Republic of Korea.
Department of Molecular Biology, College of Natural Sciences, Pusan National University, Busan 609-735, Republic of Korea.
Int J Oncol. 2015 Apr;46(4):1659-66. doi: 10.3892/ijo.2015.2857. Epub 2015 Jan 28.
Naphthazarin (Naph, DHNQ, 5,8-dihydroxy-l,4-naphthoquinone) is one of the naturally available 1,4-naphthoquinone derivatives that are well-known for their anti-inflammatory, antioxidant, antibacterial and antitumor cytotoxic effects in cancer cells. Herein, we investigated whether Naph has effects on cell cycle arrest and apoptosis in MCF-7 human breast cancer cells exposed to ionizing radiation (IR). Naph reduced the MCF-7 cell viability in a dose-dependent manner. We also found that Naph and/or IR increased the p53-dependent p21 (CIP/WAF1) promoter activity. Noteworthy, our ChIP assay results showed that Naph and IR combined treatment activated the p21 promoter via inhibition of binding of multi-domain proteins, DNMT1, UHRF1 and HDAC1. Apoptosis and cell cycle analyses demonstrated that Naph and IR combined treatment induced cell cycle arrest and apoptosis in MCF-7 cells. Herein, we showed that Naph treatment enhances IR-induced cell cycle arrest and death in MCF-7 human breast cancer cells through the p53-dependent p21 activation mechanism. These results suggest that Naph might sensitize breast cancer cells to radiotherapy by enhancing the p53-p21 mechanism activity.
萘茜（Naph，二羟基萘醌，5,8 - 二羟基 - 1,4 - 萘醌）是一种天然存在的1,4 - 萘醌衍生物，以其在癌细胞中的抗炎、抗氧化、抗菌和抗肿瘤细胞毒性作用而闻名。在此，我们研究了萘茜对暴露于电离辐射（IR）的MCF - 7人乳腺癌细胞的细胞周期阻滞和凋亡是否有影响。萘茜以剂量依赖的方式降低了MCF - 7细胞的活力。我们还发现萘茜和/或电离辐射增加了p53依赖的p21（CIP/WAF1）启动子活性。值得注意的是，我们的染色质免疫沉淀（ChIP）分析结果表明，萘茜和电离辐射联合处理通过抑制多结构域蛋白DNMT1、UHRF1和HDAC1的结合激活了p21启动子。凋亡和细胞周期分析表明，萘茜和电离辐射联合处理诱导了MCF - 7细胞的细胞周期阻滞和凋亡。在此，我们表明萘茜处理通过p53依赖的p21激活机制增强了电离辐射诱导的MCF - 7人乳腺癌细胞的细胞周期阻滞和死亡。这些结果表明，萘茜可能通过增强p53 - p21机制活性使乳腺癌细胞对放疗敏感。
