Synthetic chenodeoxycholic acid derivative HS-1200-induced apoptosis of p815 mastocytoma cells is augmented by co-treatment with lactacystin
作者:
Su Seo,
Eun Jun,
Sung Jung,
Ki-Ho Kim,
Young Lim,
Bong Park,
Jae-Kon Kim,
Sungeun Lee,
Hongsuk Suh,
Nam Kim,
Young Yoo,
期刊:
Anti-Cancer Drugs
(OVID Available online 2003)
卷期:
Volume 14,
issue 3
页码: 219-225
ISSN:0959-4973
年代: 2003
出版商: OVID
关键词: apoptosis;lactacystin;p815 mastocytoma;proteasome;synthetic chenodeoxycholic acid derivative
数据来源: OVID
摘要:
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 cytochromecto 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.
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