16-hydroxy-cleroda-3,13-dien-16,15-olide induced glioma cell autophagy via ROS generation and activation of p38 MAPK and ERK-1/2.
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.
Department of Life Science and the Institute of Biotechnology, National Dong Hwa University, Hualien 97401, Taiwan.
Varadharajan
V
Thiyagarajan
Animal Tissue Culture and Molecular Genetics Laboratory, Department of Biotechnology, School of Biotechnology and Genetic Engineering, Bharathiar University, Coimbatore 641 046, India.
Kalai Selvi
KS
Sivalingam
Animal Tissue Culture and Molecular Genetics Laboratory, Department of Biotechnology, School of Biotechnology and Genetic Engineering, Bharathiar University, Coimbatore 641 046, India.
Vijaya Padma
VP
Viswanadha
Department of Life Science and the Institute of Biotechnology, National Dong Hwa University, Hualien 97401, Taiwan. Electronic address: cfweng@mail.ndhu.edu.tw.
Ching-Feng
CF
Weng
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects*; D045744:Cell Line, Tumor; D004224:Diterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D005910:Glioma / Q000378:metabolism / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D051379:Mice; D031044:Polyalthia / Q000737:chemistry*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; D004224:Diterpenes; D017382:Reactive Oxygen Species; C072581:16-hydroxycleroda-3,13(14)-dien-15,16-olide; D048051:p38 Mitogen-Activated Protein Kinases
16-hydroxy-cleroda-3,13-dien-16,15-olide; Antioxidant enzymes; Autophagy; Brain tumor; Reactive oxygen species; p38 MAPK