title: Enhancement of radiation response in human cervical cancer cells in vitro and in vivo by arsenic trioxide (As2O3).
abstract: Arsenic trioxide (As2O3) inhibits cell growth and induces apoptosis in certain types of cancer cells including acute promyelocytic leukemia, prostate and ovarian carcinomas, but its effect on response of tumor cells to ionizing radiation has never been explored before. Here we demonstrate that As2O3 can sensitize human cervical cancer cells to ionizing radiation both in vitro and in vivo. As2O3 in combination with ionizing radiation have a synergistic effect in decreasing clonogenic survival and in the regression of established human cervical tumor xenografts. Pretreatment of the cells with As2O3 also synergistically enhanced radiation-induced apoptosis. Apoptosis of the cells by combined treatment of As2O3 and radiation was associated with reactive oxygen species generation and loss of mitochondrial membrane potential, resulting in the activation of caspase-9 and caspase-3. The combined treatment also resulted in an increased G2/M cell cycle distribution at the concentration of As2O3 which did not alter cell cycle when applied alone. These results indicate that As2O3 can synergistically enhance radiosensitivity of human cervix carcinoma cells in vitro and in vivo, suggesting a potential clinical applicability of combination treatment of As2O3 and ionizing radiation in cancer therapies.
authors.affiliation: Laboratory of Radiation Effect, Korea Cancer Center Hospital, Gongneung-Dong, Nowon-Ku, Seoul, South Korea.
authors.forename: Yong Jin
authors.initials: YJ
authors.lastname: Chun
authors.forename: In Chul
authors.initials: IC
authors.lastname: Park
authors.forename: Myung Jin
authors.initials: MJ
authors.lastname: Park
authors.forename: Sang Hyeok
authors.initials: SH
authors.lastname: Woo
authors.forename: Seok Il
authors.initials: SI
authors.lastname: Hong
authors.forename: Hee Yong
authors.initials: HY
authors.lastname: Chung
authors.forename: Tae Hwan
authors.initials: TH
authors.lastname: Kim
authors.forename: Yun Sil
authors.initials: YS
authors.lastname: Lee
authors.forename: Chang Hun
authors.initials: CH
authors.lastname: Rhee
authors.forename: Su Jae
authors.initials: SJ
authors.lastname: Lee
mesh_terms: D000818:Animals; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology* / Q000627:therapeutic use; D002277:Carcinoma / Q000628:therapy*; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D003131:Combined Modality Therapy / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004353:Drug Evaluation, Preclinical; D005260:Female; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010087:Oxides / Q000494:pharmacology* / Q000627:therapeutic use; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016896:Treatment Outcome; D014410:Tumor Stem Cell Assay; D002583:Uterine Cervical Neoplasms / Q000628:therapy*; D023041:Xenograft Model Antitumor Assays
chemical_list: D001152:Arsenicals; D010087:Oxides; D011838:Radiation-Sensitizing Agents; D000077237:Arsenic Trioxide