title: Cordycepin increases radiosensitivity in cervical cancer cells by overriding or prolonging radiation-induced G2/M arrest.
abstract: Cordycepin (3-deoxyadenosine) has many pharmacological activities. We studied the radiosensitising effect of cordycepin and the underlying mechanisms relating to cell cycle changes in two human uterine cervical cancer cell lines, ME180 and HeLa cells. Cordycepin produced concentration- and time-dependent reductions in cell viability with more pronounced effects in ME180 cells. Cells pre-treated with cordycepin showed lower cell survival than those exposed to irradiation only. Radiation-induced expression of the histone, γ-H2AX, and apoptosis were also increased following cordycepin pre-treatment. In ME180 cells, pre-treatment with cordycepin reduced radiation-induced G2/M arrest and this G2/M checkpoint override was sustained for longer than in HeLa cells, where G2/M arrest was observed earlier and more briefly, the number of HeLa cells in the G2/M phase was subsequently increased. Cordycepin produced different effects on the expression of p53 and cell cycle checkpoint proteins in these two cell lines. It can be assumed that the mechanism underlying cordycepin-mediated radiosensitisation involves multiple effects that are primarily based on the induction of p53-mediated apoptosis and modulation of the expression of cell cycle checkpoint molecules.
authors.affiliation: Department of Radiation Oncology, Chungbuk National University, College of Medicine, Cheongju, Chungbuk 28644, Republic of Korea.
authors.forename: Da Bin
authors.initials: da B
authors.lastname: Seong
authors.affiliation: Department of Radiation Oncology, Konkuk University School of Medicine, Seoul 05029, Republic of Korea.
authors.forename: Semie
authors.initials: S
authors.lastname: Hong
authors.affiliation: Department of Radiation Oncology, Chungbuk National University, College of Medicine, Cheongju, Chungbuk 28644, Republic of Korea.
authors.forename: Sridhar
authors.initials: S
authors.lastname: Muthusami
authors.affiliation: Department of Radiation Oncology, Chungbuk National University, College of Medicine, Cheongju, Chungbuk 28644, Republic of Korea.
authors.forename: Won-Dong
authors.initials: WD
authors.lastname: Kim
authors.affiliation: Department of Environmental and Tropical Medicine, Konkuk University, College of Medicine, Chungju, Chungbuk 27478, Republic of Korea.
authors.forename: Jae-Ran
authors.initials: JR
authors.lastname: Yu
authors.affiliation: Department of Radiation Oncology, Chungbuk National University, College of Medicine, Cheongju, Chungbuk 28644, Republic of Korea. Electronic address: wynpark@chungbuk.ac.kr.
authors.forename: Woo-Yoon
authors.initials: WY
authors.lastname: Park
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D003839:Deoxyadenosines / Q000494:pharmacology*; D005260:Female; D016195:G2 Phase / Q000187:drug effects / Q000528:radiation effects*; D015870:Gene Expression / Q000187:drug effects / Q000528:radiation effects; D018816:Genes, cdc / Q000187:drug effects / Q000528:radiation effects; D016158:Genes, p53 / Q000187:drug effects / Q000528:radiation effects; D006367:HeLa Cells; D006801:Humans; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D002583:Uterine Cervical Neoplasms / Q000532:radiotherapy*
chemical_list: D003839:Deoxyadenosines; D011838:Radiation-Sensitizing Agents; C058120:cordycepin
keywords: Cell cycle; Cervical cancer; Cordycepin; Cordycepin (PubChem CID 6303); Radiation