Combination treatment with arsenic trioxide and irradiation enhances apoptotic effects in U937 cells through increased mitotic arrest and ROS generation

Sheng Yow Ho, Wei Chih Chen, Hui Wen Chiu, Ching Shu Lai, How Ran Guo, Ying Jan Wang

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

Abstract

Arsenic compounds have been used as anti-cancer agents in traditional Chinese medicine. Ionizing radiation (IR) is one of the most effective tools in the clinical treatment of cancer. The induction of apoptotic cell death is a significant mechanism of tumor cells under the influence of radio-/chemotherapy, and resistance to these treatments has been linked to some cancer cell lines with a low propensity for apoptosis. A combination of different anti-tumoral treatment modalities is advantageous in limiting non-specific toxicity often observed by an exceedingly high dose of single regimen. The present study aimed at investigating the enhanced effects and mechanisms in cell cycle distribution and apoptosis of U937 cells, a human pre-monocytic leukemia cell line lacking functional p53 protein, after combination treatment with irradiation and As2O3. Our results indicated that combined treatment led to activation of cdc-2, which is related to the expression of cyclin B. In addition, combined treatment increased apoptotic cell death in U937 cells, which is correlated with the induction of mitotic arrest, the increase in intracellular reactive oxygen species (ROS) generation, the decrease in B-cell leukemia/lymphoma 2 (Bcl-2) and B-cell leukemia/lymphoma XL (Bcl-XL) levels, the loss of mitochondria membrane potential, and the activation of caspase-3. We found that combining radiation and As2O3 may be an effective strategy against p53-deficient leukemia cells.

Original languageEnglish
Pages (from-to)304-313
Number of pages10
JournalChemico-Biological Interactions
Volume179
Issue number2-3
DOIs
Publication statusPublished - May 15 2009
Externally publishedYes

Keywords

  • Apoptosis
  • Arsenic trioxide
  • Irradiation
  • Leukemia
  • Mitotic arrest

ASJC Scopus subject areas

  • Toxicology

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