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Enhancement of radiation response in human cervical cancer cells in vitro and in vivo by arsenic trioxide (As2O3)

Authors
 Yong-Jin Chun  ;  In-Chul Park  ;  Myung-Jin Park  ;  Sang-Hyeok Woo  ;  Seok-Il Hong  ;  Hee Yong Chung  ;  Tae-Hwan Kim  ;  Yun-Sil Lee  ;  Chang-Hun Rhee  ;  Su-Jae Lee 
Citation
 FEBS LETTERS, Vol.519(1-3) : 195-200, 2002 
Journal Title
FEBS LETTERS
ISSN
 0014-5793 
Issue Date
2002
MeSH
Animals ; ArsenicTrioxide ; Arsenicals/pharmacology* ; Arsenicals/therapeutic use ; Carcinoma/therapy* ; CellSurvival/drug effects ; CellSurvival/radiationeffects ; Combined Modality Therapy/methods* ; Dose-ResponseRelationship, Drug ; Dose-ResponseRelationship,Radiation ; Drug Evaluation, Preclinical ; Female ; HeLaCells ; Humans ; Mice ; Mice, Nude ; Neoplasm Transplantation ; Oxides/pharmacology* ; Oxides/therapeutic use ; Radiation-Sensitizing Agents/pharmacology* ; Radiation-Sensitizing Agents/therapeutic use ; Treatment Outcome ; Tumor StemCellAssay ; UterineCervicalNeoplasms/therapy* ; Xenograft Model Antitumor Assays
Keywords
Arsenic trioxide ; Radiosensitivity ; Cervical cancer cells ; Reactive oxygen species ; Mitochondrial membrane potential
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.
Files in This Item:
T200208053.pdf Download
DOI
10.1016/S0014-5793(02)02765-5
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Radiation Oncology (방사선종양학교실) > 1. Journal Papers
Yonsei Authors
Lee, Yun Sil(이윤실)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/144214
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