Abstract |
This study is aimed at investigating the effect of arsenic trioxide (ATO) on p53 null human osteosarcoma MG63 cells and the mechanisms underlying the effect. Apoptotic cells were detected by flow cytometry with Annexin-V-FITC/PI dual staining. Intracellular ROS was measured by flow cytometry using a cell-based ROS assay kit. Catalase activity and mRNAs were analyzed by ELISA and real-time qRT-PCR, respectively. Apoptosis and intracellular ROS of MG63 cells increased in a dose-dependent manner following arsenic treatments. Both were prevented by the presence of the anti-oxidative reagent N-acetyl-L: -cysteine (NAC) or catalase (CAT). Furthermore, the activity and mRNA of catalase were decreased strikingly following arsenic exposure. The present study indicates that p53 null osteosarcoma MG63 cells are susceptible to the ATO; the inhibition of catalase and the resulted intracellular ROS accumulation are an important molecular mechanism under which ATO induces apoptosis of p53-deficient osteosarcoma cells.
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Authors | Yang Wang, Yudan Wei, Haiying Zhang, Yanfen Shi, Yulin Li, Ronggui Li |
Journal | Medical oncology (Northwood, London, England)
(Med Oncol)
Vol. 29
Issue 2
Pg. 1328-34
(Jun 2012)
ISSN: 1559-131X [Electronic] United States |
PMID | 21308489
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents
- Arsenicals
- Oxides
- RNA, Messenger
- Reactive Oxygen Species
- TP53 protein, human
- Tumor Suppressor Protein p53
- Catalase
- Glutathione
- Arsenic Trioxide
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Topics |
- Antineoplastic Agents
(pharmacology)
- Apoptosis
(drug effects)
- Arsenic Trioxide
- Arsenicals
(pharmacology)
- Blotting, Western
- Bone Neoplasms
(drug therapy, metabolism, pathology)
- Catalase
(antagonists & inhibitors, genetics, metabolism)
- Cell Line, Tumor
- Flow Cytometry
- Glutathione
(metabolism)
- Humans
- Osteosarcoma
(drug therapy, metabolism, pathology)
- Oxides
(pharmacology)
- RNA, Messenger
(genetics)
- Reactive Oxygen Species
(metabolism)
- Real-Time Polymerase Chain Reaction
- Reverse Transcriptase Polymerase Chain Reaction
- Tumor Suppressor Protein p53
(deficiency)
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