Seo Su Yeong, Jun Eun Joo, Jung Sung Moon, Kim Ki-Ho, Lim Young Jin, Park Bong Soo, Kim Jae-Kon, Lee Sungeun, Suh Hongsuk, Kim Nam Deuk, Yoo Young Hyun
Department of Microbiology and Immunology, Dong-A University College of Medicine and Institute of Medical Science, Seo Gu, Busan, South Korea.
Anticancer Drugs. 2003 Mar;14(3):219-25. doi: 10.1097/00001813-200303000-00005.
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 microM induced apoptosis of p815 cells. Reduction of mitochondrial membrane potential, the release of cytochrome 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 microM HS-1200 or 1 microM 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.
研究了一种合成鹅去氧胆酸衍生物HS - 1200对p815肥大细胞瘤细胞系的抗肿瘤活性。我们提供了几条证据表明，35微摩尔的HS - 1200可诱导p815细胞凋亡。证明了线粒体膜电位降低、细胞色素释放到细胞质、半胱天冬酶 - 3激活、核浓缩、聚（ADP - 核糖）聚合酶裂解产物生成、DNA片段化以及核浓缩。重要的是，HS - 1200抑制蛋白酶体活性。接下来，进行了HS - 1200或蛋白酶体抑制剂乳胞素的联合治疗。虽然单独使用20微摩尔的HS - 1200或1微摩尔的乳胞素轻微诱导凋亡，但它们的联合治疗显著增强了凋亡程度。HS - 1200和乳胞素的联合疗法可能是一种降低治疗相关毒性程度和严重性的治疗策略。
