Mechanisms of 2-methoxyestradiol-induced apoptosis and G2/M cell-cycle arrest of nasopharyngeal carcinoma cells
| Autor: | Yuen Kit Cheng, Nai Ki Mak, Choi-Man Ting, Maria Li Lung, Yee-Man Lee, Ricky N S Wong, Tai-Ping Fan |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
MAPK/ERK pathway
G2 Phase Cancer Research Cell cycle checkpoint MAP Kinase Signaling System Antineoplastic Agents Apoptosis Superoxide dismutase chemistry.chemical_compound Cell Line Tumor medicine Humans 2-Methoxyestradiol Cell Proliferation biology Estradiol Kinase Superoxide Superoxide Dismutase JNK Mitogen-Activated Protein Kinases Nasopharyngeal Neoplasms Flow Cytometry Molecular biology Cell biology Oxidative Stress Oncology chemistry Cell culture biology.protein Cell Division medicine.drug |
| Zdroj: | Cancer letters. 268(2) |
| ISSN: | 1872-7980 |
| Popis: | 2-Methoxyestradiol (2ME2) is an endogenous metabolite of 17beta-estradiol (E(2)). This study aims to examine the anti-tumour activities of 2ME2 on the poorly differentiated HONE-1 NPC cell line. At the concentration of 1 microM, 2ME2 was found to induce a short-term reversible G2/M cell-cycle arrest. Further 10-fold increase to 10 microM, 2ME2 induced both irreversible G2/M phase cell-cycle arrest and apoptosis. Induction of apoptosis and G2/M cell-cycle arrest was due to oxidative stress as both apoptosis and the proportion of cells arresting at G2/M phase could be reduced by the superoxide dismutase (SOD) mimetic, TEMPO. Induction of apoptosis was accompanied with proteolytic cleavage of caspase-9 and -3, but not caspase-8. Kinetics studies revealed that 2ME2 induced a time-dependent inhibition of extracellular signal-regulated protein kinase (ERK) and an activation of c-jun N-terminal kinases (JNKs). The chemical inhibitor of JNKs, SP600125, was found to reduce 2ME2-induced apoptosis of the HONE-1 cells. Confocal microscopy revealed that the induction of G2/M cell-cycle arrest was associated with the presence of immunoreactivity of p-cdc2 (Tyr15) in the nucleus. The G2/M cell-cycle arrest is also correlated with an increased level of inactive p-cdc25C (Ser216) in 2ME2-treated HONE-1 cells. Results from this study indicate that production of superoxide anions might be involved in 2ME2-induced apoptosis and G2/M cell-cycle arrest of the HONE-1 cells. |
| Databáze: | OpenAIRE |
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