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

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

Research output: Contribution to journalArticlepeer-review

70 Scopus citations


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.

Original languageEnglish
Pages (from-to)195-200
Number of pages6
JournalFEBS Letters
Issue number1-3
StatePublished - 22 May 2002

Bibliographical note

Funding Information:
We thank Soo-Kwan Kim and Kyung-Joong Kim for their expert technical assistance. This work was supported by a Nuclear R&D Program from the Ministry of Science and Technology in Korea.


  • Arsenic trioxide
  • Cervical cancer cells
  • Mitochondrial membrane potential
  • Radiosensitivity
  • Reactive oxygen species


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