Thiyagarajan Varadharajan, Sivalingam Kalai Selvi, Viswanadha Vijaya Padma, Weng Ching-Feng
Department of Life Science and the Institute of Biotechnology, National Dong Hwa University, Hualien 97401, Taiwan.
Animal Tissue Culture and Molecular Genetics Laboratory, Department of Biotechnology, School of Biotechnology and Genetic Engineering, Bharathiar University, Coimbatore 641 046, India.
Environ Toxicol Pharmacol. 2016 Jul;45:202-11. doi: 10.1016/j.etap.2016.06.005. Epub 2016 Jun 6.
16-hydroxy-cleroda-3,13-dien-16,15-olide (HCD), a natural product isolated from medicinal plant Polyalthia longifolia exhibits anticancer activity through caspase-independent apoptosis in brain tumors, as previously reported. This study further attempted to investigate the involvement of HCD-induced autophagy in brain tumor cell lines neuroblastoma N18 and glioma C6 through the induction of reactive oxygen species (ROS) and the activation of p38 and ERK-1/2 pathway. The results demonstrated that HCD increased the hyper-generation of ROS and decreased cellular antioxidant enzymes, such as superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GPx), and glutathione s transferase (GST). Furthermore, HCD increased the expressions of autophagic marker proteins LC3-II and Beclin-1 in a time- and dose-dependent manner. Additionally, HCD was found to significantly induce p-p38 MAPK and p-ERK-1/2 proteins by Western blot, which implies that HCD is a potential therapeutic anticancer agent that exerts its activity through inducing ROS-mediation for the autophagy of brain tumor cells.
16-羟基-克罗烷-3,13-二烯-16,15-内酯（HCD）是一种从药用植物长叶暗罗中分离出的天然产物，如先前报道的那样，它通过不依赖半胱天冬酶的凋亡在脑肿瘤中发挥抗癌活性。本研究进一步试图通过诱导活性氧（ROS）以及激活p38和ERK-1/2通路，来探究HCD诱导的自噬在脑肿瘤细胞系神经母细胞瘤N18和胶质瘤C6中的作用。结果表明，HCD增加了ROS的过度生成，并降低了细胞抗氧化酶的水平，如超氧化物歧化酶（SOD）、谷胱甘肽（GSH）、谷胱甘肽过氧化物酶（GPx）和谷胱甘肽S-转移酶（GST）。此外，HCD以时间和剂量依赖性方式增加了自噬标记蛋白LC3-II和Beclin-1的表达。另外，通过蛋白质印迹法发现HCD能显著诱导p-p38 MAPK和p-ERK-1/2蛋白，这表明HCD是一种潜在的治疗性抗癌药物，它通过诱导ROS介导脑肿瘤细胞自噬来发挥其活性。
