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Combination treatment with arsenic trioxide and irradiation enhances apoptotic effects in U937 cells through increased mitotic arrest and ROS generation.
- Source :
-
Chemico-biological interactions [Chem Biol Interact] 2009 May 15; Vol. 179 (2-3), pp. 304-13. Date of Electronic Publication: 2008 Dec 30. - Publication Year :
- 2009
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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 As(2)O(3). 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 As(2)O(3) may be an effective strategy against p53-deficient leukemia cells.
- Subjects :
- Arsenic Trioxide
Caspases metabolism
Cell Cycle drug effects
Cell Division drug effects
Cell Division radiation effects
Cyclin A biosynthesis
Cyclin A drug effects
Cyclin A radiation effects
Cyclin B biosynthesis
Cyclin B drug effects
Cyclin B radiation effects
Cytochromes c drug effects
Cytochromes c metabolism
Cytochromes c radiation effects
Drug Screening Assays, Antitumor
G2 Phase drug effects
G2 Phase radiation effects
Humans
Mitochondrial Membranes drug effects
Mitochondrial Membranes metabolism
Mitochondrial Membranes radiation effects
Radiation, Ionizing
Tumor Cells, Cultured
Tumor Suppressor Protein p53 biosynthesis
Tumor Suppressor Protein p53 drug effects
Tumor Suppressor Protein p53 radiation effects
U937 Cells
Antineoplastic Agents pharmacology
Apoptosis drug effects
Apoptosis radiation effects
Arsenicals pharmacology
Mitosis drug effects
Mitosis radiation effects
Oxides pharmacology
Reactive Oxygen Species metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1872-7786
- Volume :
- 179
- Issue :
- 2-3
- Database :
- MEDLINE
- Journal :
- Chemico-biological interactions
- Publication Type :
- Academic Journal
- Accession number :
- 19159621
- Full Text :
- https://doi.org/10.1016/j.cbi.2008.12.015