Synthetic chenodeoxycholic acid derivative HS-1200-induced apoptosis of p815 mastocytoma cells is augmented by co-treatment with lactacystin
Synthetic chenodeoxycholic acid derivative HS-1200-induced apoptosis of p815 mastocytoma cells is augmented by co-treatment with lactacystin
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DOI：
10.1097/00001813-200303000-00005
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发表时间：
2003-03
影响因子：
2.3
通讯作者：
S. Seo;E. Jun;S. Jung;Ki-ho Kim;Y. Lim;B. Park;Jae-Kon Kim;Sungeun Lee;H. Suh;N. Ki
中科院分区：
文献类型：
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作者：
S. Seo;E. Jun;S. Jung;Ki-ho Kim;Y. Lim;B. Park;Jae-Kon Kim;Sungeun Lee;H. Suh;N. Ki
研究了合成的鹅去氧胆酸衍生物HS-1200对p815肥大细胞瘤细胞系的抗肿瘤活性。我们提出了几条证据表明，HS-1200在35 μM诱导p815细胞凋亡。线粒体膜电位降低，细胞色素c释放到胞质溶胶中，caspase-3活化，核浓缩，产生聚（ADP-核糖）聚合酶切割，DNA片段化和核浓缩。重要的是，HS-1200抑制蛋白酶体活性。接下来，进行HS-1200或蛋白酶体抑制剂lactacystin的组合治疗。20 μM HS-1200和1 μM lactacystin单独处理时，细胞凋亡率较低，但二者联合处理时，细胞凋亡率明显增加。HS-1200和lactacystin的联合治疗可能是降低治疗相关毒性的程度和严重程度的潜在治疗策略。
The antitumor activity of a synthetic chenodeoxycholic acid derivative, HS-1200, on the p815 mastocytoma cell line was investigated. We present several lines of evidence indicating that HS-1200 at 35 μM induced apoptosis of p815 cells. Reduction of mitochondrial membrane potential, the release of cytochrome c to cytosol, activation of caspase-3, nuclear condensation, production of poly(ADP-ribose) polymerase cleavage, generation of DNA fragmentation and nuclear condensation were demonstrated. Importantly, HS-1200 inhibited proteasome activity. Next, the combination treatment of HS-1200 or a proteasome inhibitor lactacystin was undertaken. Although the single treatment of 20 μM HS-1200 or 1 μM lactacystin induced apoptosis slightly, the combination treatment of them augmented prominently the extent of apoptosis. The combination therapy of HS-1200 and lactacystin could be potentially a therapeutic strategy reducing the extent and severity of treatment-related toxicity.