title: Sensitization of the apoptotic effect of gamma-irradiation in genistein-pretreated CaSki cervical cancer cells.
abstract: Radiotherapy is currently applied in the treatment of human cancers. We studied whether genistein would enhance the radiosensitivity and explored its precise molecular mechanism in cervical cancer cells. After co-treatment with genistein and irradiation, the viability, cell cycle analysis, and apoptosis signaling cascades were elucidated in CaSki cells. The viability was decreased by co-treatment with genistein and irradiation compared with irradiation treatment alone. Treatment with only gamma-irradiation led to cell cycle arrest at the G1 phase. On the other hand, co-treatment with genistein and gamma-irradiation caused a decrease in the G1 phase and a concomitant increase up to 56% in the number of G2 phase. In addition, cotreatment increased the expression of p53 and p21, and Cdc2- tyr-15-p, supporting the occurrence of G2/M arrest. In general, apoptosis signaling cascades were activated by the following events: release of cytochrome c, upregulation of Bax, downregulation of Bcl-2, and activation of caspase-3 and -8 in the treatment of genistein and irradiation. Apparently, co-treatment downregulated the transcripts of E6*I, E6*II, and E7. Genistein also stimulated irradiation-induced intracellular reactive oxygene, species (ROS) production, and co-treatment-induced apoptosis was inhibited by the antioxidant N-acetylcysteine, suggesting that apoptosis has occurred through the increase in ROS by genistein and gamma-irradiation in cervical cancer cells. Gamma-irradiation increased cyclooxygenase-1 (COX-2) expression, whereas the combination with genistein and gamma-irradiation almost completely prevented irradiation-induced COX-2 expression and PGE2 production. Co-treatment with genistein and gamma-irradiation inhibited proliferation through G2/M arrest and induced apoptosis via ROS modulation in the CaSki cancer cells.
authors.affiliation: Department of Bioscience and Biotechnology, Konkuk University, Seoul 143-701, Korea.
authors.forename: Jang-In
authors.initials: JI
authors.lastname: Shin
authors.forename: Jung-Hyun
authors.initials: JH
authors.lastname: Shim
authors.forename: Ki-Hong
authors.initials: KH
authors.lastname: Kim
authors.forename: Hee-Sook
authors.initials: HS
authors.lastname: Choi
authors.forename: Jae-Wha
authors.initials: JW
authors.lastname: Kim
authors.forename: Hee-Gu
authors.initials: HG
authors.lastname: Lee
authors.forename: Bo-Yeon
authors.initials: BY
authors.lastname: Kim
authors.forename: Sue-Nie
authors.initials: SN
authors.lastname: Park
authors.forename: Ok-Jin
authors.initials: OJ
authors.lastname: Park
authors.forename: Do-Young
authors.initials: DY
authors.lastname: Yoon
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D015232:Dinoprostone / Q000235:genetics / Q000378:metabolism; D005260:Female; D005720:Gamma Rays; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000528:radiation effects; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D011836:Radiation Tolerance; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D002583:Uterine Cervical Neoplasms / Q000628:therapy*
chemical_list: D051017:Apoptosis Regulatory Proteins; D011838:Radiation-Sensitizing Agents; D017382:Reactive Oxygen Species; D019833:Genistein; D051546:Cyclooxygenase 2; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate