title: Crocodile choline from Crocodylus siamensis induces apoptosis of human gastric cancer.
abstract: Crocodile choline, an active compound isolated from Crocodylus siamensis, was found to exert potent anti-cancer activities against human gastric cancer cells in vitro and in vivo. Our study revealed that crocodile choline led to cell cycle arrest at the G2/M phase through attenuating the expressions of cyclins, Cyclin B1, and CDK-1. Furthermore, crocodile choline accelerated apoptosis through the mitochondrial apoptotic pathway with the decrease in mitochondrial membrane potential, the increase in reactive oxygen species production and Bax/Bcl-2 ratio, and the activation of caspase-3 along with the release of cytochrome c. In addition, this study, for the first time, shows that Notch pathway is remarkably deregulated by crocodile choline. The combination of crocodile choline and Notch1 short interfering RNA led to dramatically increased cytotoxicity than observed with either agent alone. Notch1 short interfering RNA sensitized and potentiated the capability of crocodile choline to suppress the cell progression and invasion of gastric cancer. Taken together, these data suggested that crocodile choline was a potent progression inhibitor of gastric cancer cells, which was correlated with mitochondrial apoptotic pathway and Notch pathway. Combining Notch1 inhibitors with crocodile choline might represent a novel approach for gastric cancer.
authors.affiliation: 1 State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, China.|2 Key Laboratory of the Ministry of Education for Coastal and Wetland Ecosystems, School of Life Sciences, Xiamen University, Xiamen, China.
authors.forename: Xiao-Mei
authors.initials: XM
authors.lastname: Mao
authors.affiliation: 1 State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, China.|2 Key Laboratory of the Ministry of Education for Coastal and Wetland Ecosystems, School of Life Sciences, Xiamen University, Xiamen, China.
authors.forename: Qi-Rui
authors.initials: QR
authors.lastname: Fu
authors.affiliation: 1 State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, China.|2 Key Laboratory of the Ministry of Education for Coastal and Wetland Ecosystems, School of Life Sciences, Xiamen University, Xiamen, China.
authors.forename: Hua-Liang
authors.initials: HL
authors.lastname: Li
authors.affiliation: 1 State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, China.|2 Key Laboratory of the Ministry of Education for Coastal and Wetland Ecosystems, School of Life Sciences, Xiamen University, Xiamen, China.
authors.forename: Ya-Hui
authors.initials: YH
authors.lastname: Zheng
authors.affiliation: 1 State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, China.|2 Key Laboratory of the Ministry of Education for Coastal and Wetland Ecosystems, School of Life Sciences, Xiamen University, Xiamen, China.
authors.forename: Shu-Ming
authors.initials: SM
authors.lastname: Chen
authors.affiliation: 1 State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, China.|2 Key Laboratory of the Ministry of Education for Coastal and Wetland Ecosystems, School of Life Sciences, Xiamen University, Xiamen, China.
authors.forename: Xin-Yi
authors.initials: XY
authors.lastname: Hu
authors.affiliation: 1 State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, China.|2 Key Laboratory of the Ministry of Education for Coastal and Wetland Ecosystems, School of Life Sciences, Xiamen University, Xiamen, China.
authors.forename: Qing-Xi
authors.initials: QX
authors.lastname: Chen
authors.affiliation: 3 The First Affiliated Hospital of Xiamen University, Xiamen, China.
authors.forename: Qiong-Hua
authors.initials: QH
authors.lastname: Chen
mesh_terms: D000489:Alligators and Crocodiles / Q000378:metabolism; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols; D017209:Apoptosis / Q000187:drug effects*; D016203:CDC2 Protein Kinase; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D002794:Choline / Q000008:administration & dosage*; D056744:Cyclin B1 / Q000096:biosynthesis; D018844:Cyclin-Dependent Kinases / Q000096:biosynthesis; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008928:Mitochondria / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D051881:Receptor, Notch1 / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D013274:Stomach Neoplasms / Q000188:drug therapy*; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis
chemical_list: D056744:Cyclin B1; C497761:NOTCH1 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D051881:Receptor, Notch1; D051028:bcl-2-Associated X Protein; D016203:CDC2 Protein Kinase; C528899:CDK1 protein, human; D018844:Cyclin-Dependent Kinases; D002794:Choline
keywords: Crocodile choline; Notch; apoptosis; gastric cancer; mitochondria