title: Sensitization of cancer cells to radiation by selenadiazole derivatives by regulation of ROS-mediated DNA damage and ERK and AKT pathways.
abstract: X-ray-based radiotherapy represents one of the most effective ways in treating human cancers. However, radioresistance and side effect remain as the most challenging issue. This study describes the design and application of novel selenadiazole derivatives as radiotherapy sensitizers to enhance X-ray-induced inhibitory effects on A375 human melanoma and Hela human cervical carcinoma cells. The results showed that, pretreatment of the cells with selenadiazole derivatives dramatically enhance X-ray-induced growth inhibition and colony formation. Flow cytometry analysis indicates that the sensitization by selenadiazole derivatives was mainly caused by induction of G2/M cell cycle arrest. Results of Western blotting demonstrated that the combined treatment-induced A375 cells growth inhibition was achieved by triggering reactive oxygen species-mediated DNA damage involving inactivation of AKT and MAPKs. Further investigation revealed that selenadiazole derivative in combination with X-ray could synergistically inhibit the activity of thioredoxin reductase-1 in A375 cells. Taken together, these results suggest that selenadiazole derivatives can act as novel radiosensitizer with potential application in combating human cancers.
authors.affiliation: Department of Chemistry, Jinan University, Guangzhou 510632, China; Wu Jing Zong Dui Hospital of Guangdong Province, Guangzhou, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xie
authors.affiliation: Department of Chemistry, Jinan University, Guangzhou 510632, China.
authors.forename: Yangliang
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Chemistry, Jinan University, Guangzhou 510632, China.
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Lan
authors.affiliation: Department of Chemistry, Jinan University, Guangzhou 510632, China.
authors.forename: Liye
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Chemistry, Jinan University, Guangzhou 510632, China.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Zheng
authors.affiliation: Department of Chemistry, Jinan University, Guangzhou 510632, China.
authors.forename: Yuanwei
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Department of Chemistry, Jinan University, Guangzhou 510632, China. Electronic address: tchentf@jnu.edu.cn.
authors.forename: Tianfeng
authors.initials: T
authors.lastname: Chen
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D001393:Azoles / Q000008:administration & dosage / Q000138:chemical synthesis; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004249:DNA Damage / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000528:radiation effects; D006367:HeLa Cells; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000528:radiation effects*; D008545:Melanoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D051058:Oncogene Protein v-akt / Q000378:metabolism; D016566:Organoselenium Compounds / Q000138:chemical synthesis / Q000494:pharmacology*; D011810:Quinoxalines / Q000138:chemical synthesis / Q000494:pharmacology*; D011836:Radiation Tolerance / Q000187:drug effects* / Q000528:radiation effects; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage / Q000138:chemical synthesis; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D016896:Treatment Outcome
chemical_list: D001393:Azoles; D016566:Organoselenium Compounds; D011810:Quinoxalines; D011838:Radiation-Sensitizing Agents; D017382:Reactive Oxygen Species; D051058:Oncogene Protein v-akt
keywords: Radiotherapy; Selenadiazole derivative; Signaling; Thioredoxin reductase