title: Activating AKT to inhibit JNK by troxerutin antagonizes radiation-induced PTEN activation.
abstract: Radiotherapy is one of the most effective non-surgical treatments for many tumors. However, radiation damage remains a major negative consequence of radiotherapy. At present, radio-protective effect of troxerutin has been confirmed, but the mechanism of this radioprotection has not been elucidated. Here, this study showed that troxerutin protected thymus tissue of irradiated mice, and its radio-protective effect on thymocytes was significant in the range of 0.625-10μg/ml. Troxerutin significantly inhibited apoptosis of irradiated thymocytes at the concentration of 10μg/ml. Computer-aided drug design was used to investigate potential candidate targets for troxerutin, and an excellent correlation was identified between troxerutin and AKT (Pharm mapper and KEGG signal pathway). Troxerutin inhibited the activation of PTEN to stimulate AKT, which in turn prevented the activation of JNK to protect cells. Our results showed that troxerutin enhanced radioprotection at least partially by activating AKT to inhibit the activation of JNK.
authors.affiliation: Department of Pharmacy, Xinxiang Medical University, Xinxiang, Henan 453003, China. Electronic address: 13273730271@163.com.
authors.forename: Ping
authors.initials: P
authors.lastname: Xu
authors.affiliation: Synthetic Biology Remaking Engineering and Application Laboratory, Xinxiang Medical University, Xinxiang, Henan 453003, China.
authors.forename: Wen-Bo
authors.initials: WB
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, Xinxiang Medical University, Xinxiang, Henan 453003, China.
authors.forename: Xin-Hua
authors.initials: XH
authors.lastname: Cai
authors.affiliation: Department of Pharmacy, Xinxiang Medical University, Xinxiang, Henan 453003, China.
authors.forename: Pei-Yong
authors.initials: PY
authors.lastname: Qiu
authors.affiliation: Department of Pharmacy, Xinxiang Medical University, Xinxiang, Henan 453003, China.
authors.forename: Ming-Hua
authors.initials: MH
authors.lastname: Hao
authors.affiliation: Institute of Radiation Medicine, Military Medical Sciences, Beijing 100850, China.
authors.forename: Dan-Dan
authors.initials: DD
authors.lastname: Lu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004789:Enzyme Activation / Q000187:drug effects / Q000528:radiation effects; D006896:Hydroxyethylrutoside / Q000031:analogs & derivatives* / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D008297:Male; D051379:Mice; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D013950:Thymus Gland / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects
chemical_list: D006896:Hydroxyethylrutoside; D011837:Radiation-Protective Agents; C005865:troxerutin; D051057:Proto-Oncogene Proteins c-akt; D048031:JNK Mitogen-Activated Protein Kinases; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse
keywords: AKT; JNK; PTEN; Thymus cell; Troxerutin