title: Cordycepin induced MA-10 mouse Leydig tumor cell apoptosis by regulating p38 MAPKs and PI3K/AKT signaling pathways.
abstract: The p38 MAPKs play important roles in the regulation of balance between cell survival and cell death on the development of various cancers. However, the roles of p38 MAPKs regulating apoptotic effects on Leydig tumor cells remain unclear. In the present study, we showed that cordycepin (3'-deoxyadenosine) selectively induced apoptosis in MA-10 mouse Leydig tumor cells through regulating the p38 MAPK and PI3K/AKT signaling pathways. Cordycepin reduced viability in MA-10, TM4, and NT2/D1 cells, but not cause cell death of primary mouse Leydig cells on moderate concentration. Cordycepin increased reactive oxygen species (ROS) levels, which is associated with the induction of apoptosis as characterized by positive Annexin V binding, activation of caspase-3, and cleavage of PARP. Inhibition of p38 MAPKs activity by SB203580 significantly prevented cordycepin-induced apoptosis in MA-10 cells. Co-treatment with wortmannin or the autophagy inhibitor 3-methyladenine (3-MA) elevated levels of apoptosis in cordycepin-treated MA-10 cells. Moreover, cordycepin activated p53, p21 and TGFß; and downregulated CDK2. The antitumour activity of cordycepin-treated MA-10 cells was significantly distinct in severe combined immunodeficiency (SCID) mice in vivo. These results suggested that cordycein is a highly selective treatment to induce MA-10 cells apoptosis via p38 MAPKs signaling.
authors: Institute of Basic Medical Sciences, College of Medicine, National Chen Kung University, Tainan, Taiwan, Republic of China.|Department of Cell Biology and Anatomy, College of Medicine, National Chen Kung University, Tainan, Taiwan, Republic of China.
authors: Bo-Syong
authors: BS
authors: Pan
authors: Institute of Basic Medical Sciences, College of Medicine, National Chen Kung University, Tainan, Taiwan, Republic of China.|Department of Cell Biology and Anatomy, College of Medicine, National Chen Kung University, Tainan, Taiwan, Republic of China.
authors: Yang-Kao
authors: YK
authors: Wang
authors: Institute of Basic Medical Sciences, College of Medicine, National Chen Kung University, Tainan, Taiwan, Republic of China.|Department of Cell Biology and Anatomy, College of Medicine, National Chen Kung University, Tainan, Taiwan, Republic of China.
authors: Meng-Shao
authors: MS
authors: Lai
authors: Department of Cell Biology and Anatomy, College of Medicine, National Chen Kung University, Tainan, Taiwan, Republic of China.
authors: Yi-Fen
authors: YF
authors: Mu
authors: Institute of Basic Medical Sciences, College of Medicine, National Chen Kung University, Tainan, Taiwan, Republic of China.|Department of Cell Biology and Anatomy, College of Medicine, National Chen Kung University, Tainan, Taiwan, Republic of China.
authors: Bu-Miin
authors: BM
authors: Huang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D003839:Deoxyadenosines / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D007984:Leydig Cell Tumor / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D051058:Oncogene Protein v-akt / Q000378:metabolism*; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D003839:Deoxyadenosines; D058539:Phosphatidylinositol 3-Kinase; D051058:Oncogene Protein v-akt; C058120:cordycepin