Enhancement of radiation response in human cervical cancer cells in vitro and in vivo by arsenic trioxide (As2O3).
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.
Chun
Yong Jin
YJ
Laboratory of Radiation Effect, Korea Cancer Center Hospital, Gongneung-Dong, Nowon-Ku, Seoul, South Korea.
Park
In Chul
IC
Park
Myung Jin
MJ
Woo
Sang Hyeok
SH
Hong
Seok Il
SI
Chung
Hee Yong
HY
Kim
Tae Hwan
TH
Lee
Yun Sil
YS
Rhee
Chang Hun
CH
Lee
Su Jae
SJ
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
D001152:Arsenicals; D010087:Oxides; D011838:Radiation-Sensitizing Agents; D000077237:Arsenic Trioxide