title: ROS-mediated autophagy induced by dysregulation of lipid metabolism plays a protective role in colorectal cancer cells treated with gambogic acid.
abstract: Gambogic acid (GA), the main active component of gamboge resin, has potent antitumor activity both in vivo and in vitro. However, the underlying molecular mechanisms remain unclear. In this study, we found that GA could initiate autophagy in colorectal cancer cells, and inhibition of the autophagy process accelerated the effect of proliferative inhibition and apoptotic cell death induced by GA, implying a protective role of autophagy. Two-dimensional electrophoresis-based proteomics showed that GA treatment altered the expression of multiple proteins involved in redox signaling and lipid metabolism. Functional studies revealed that GA-induced dysregulation of lipid metabolism could activate 5-lipoxygenase (5-LOX), resulting in intracellular ROS accumulation, followed by inhibition of Akt-mTOR signaling and autophagy initiation. Finally, results using a xenograft model suggested ROS-induced autophagy protect against the antitumor effect of GA. Taken together, these data showed new biological activities of GA against colorectal cancer underlying the protective role of ROS-induced autophagy. This study will provide valuable insights for future studies regarding the anticancer mechanisms of GA.
authors.affiliation: Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of science and Technology, Wuhan, People's Republic of China.
authors.forename: Haiyuan
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Biology, and Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing, China.
authors.forename: Yunlong
authors.initials: Y
authors.lastname: Lei
authors.affiliation: Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of science and Technology, Wuhan, People's Republic of China.
authors.forename: Ping
authors.initials: P
authors.lastname: Yuan
authors.affiliation: Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of science and Technology, Wuhan, People's Republic of China.
authors.forename: Lingjun
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of science and Technology, Wuhan, People's Republic of China.
authors.forename: Chao
authors.initials: C
authors.lastname: Luo
authors.affiliation: Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of science and Technology, Wuhan, People's Republic of China.
authors.forename: Rui
authors.initials: R
authors.lastname: Gao
authors.affiliation: Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of science and Technology, Wuhan, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Tian
authors.affiliation: Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of science and Technology, Wuhan, People's Republic of China.
authors.forename: Zuohua
authors.initials: Z
authors.lastname: Feng
authors.affiliation: Monash University, Department of Biochemistry and Molecular Biology, Clayton, Victoria, Australia.
authors.forename: Edouard C
authors.initials: EC
authors.lastname: Nice
authors.affiliation: Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of science and Technology, Wuhan, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Sun
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects* / Q000502:physiology; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects* / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D044004:Xanthones / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D044004:Xanthones; C052659:gambogic acid