Arsenic Trioxide Induces Apoptosis in Uveal Melanoma Cells Through the Mitochondrial Pathway

被引:15
|
作者
Chen, Miao-Ju [1 ]
Yang, Pei-Yu [1 ]
Ye, Yi-Zhen [1 ]
Hu, Dan-Ning [1 ,2 ]
Chen, Ming-Feng [1 ,3 ]
机构
[1] Show Chwan Mem Hosp, Dept Med Res, Changhua 500, Taiwan
[2] New York Med Coll, New York Eye & Ear Infirm, New York, NY 10003 USA
[3] China Med Univ, Grad Inst Chinese Med Sci, Taichung 40402, Taiwan
来源
AMERICAN JOURNAL OF CHINESE MEDICINE | 2010年 / 38卷 / 06期
关键词
Uveal Melanoma; Arsenic Trioxide; Apoptosis; Bcl-2; Caspase; Cytochrome c; ACUTE PROMYELOCYTIC LEUKEMIA; PHASE-II TRIAL; IN-VITRO; METASTATIC MELANOMA; CYTOCHROME-C; ASCORBIC-ACID; DIFFERENTIATION; GROWTH; CANCER; BCL-2;
D O I
10.1142/S0192415X10008524
中图分类号
R [医药、卫生];
学科分类号
10 ;
摘要
Uveal melanoma, the most common primary intraocular malignancy in adults, is highly resistant to most chemotherapeutic drugs. Arsenic trioxide (ATO) is known to inhibit ocular melanoma cell growth. However, the effects of ATO on human uveal melanoma cells are poorly understood. Therefore, this study evaluated the mechanisms of ATO and its inhibiting effects on a human uveal melanoma cell line (SP6.5). An MTT assay indicated that, compared to human fibroblasts, ATO had a stronger inhibiting effect on SP6.5 cell proliferation in a dose-and time-dependent manner. The apoptosis ratio in SP6.5 cells, which was indicated by cell DNA fragmentation, was 4.1-to 7.7-fold higher after ATO-treatment. The ATO treatment substantially increased the activities of caspase-3 and caspase-9, but not of caspase-8. These findings were consistent with the protein expression observed by Western blots. ATO also significantly enhanced expression of Bax and cytochrome c proteins but suppressed those of Bcl-2. Therefore, ATO-induced apoptosis in uveal melanoma cells occurs mainly through the mitochondrial pathway rather than through the death receptor pathway. This report is the first to evaluate the complete mitochondria-dependent apoptotic pathway of ATO in uveal melanoma cells. These results can be used to improve the clinical effectiveness of ATO treatment for uveal melanoma.
引用
收藏
页码:1131 / 1142
页数:12
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