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海绵三萜化合物Jaspolide B体外抗白血病 (HL-60细胞) 活性研究

李敏, 魏少荫, 唐生安, 林文翰, 崔景荣*   

  1. 北京大学 天然药物及仿生药物国家重点实验室, 北京 100083

  • 收稿日期:2007-10-16 修回日期:2008-01-10 出版日期:2008-03-15 发布日期:2008-03-15
  • 通讯作者: 崔景荣*

Antileukemic activity of jaspolide B, an isomalabaricane-type triterpene from marine sponge Jaspis sp. on human promyeloleukemic HL-60 cells

Min Li, Shao-Yin Wei, Sheng-An Tang, Wen-Han Lin, Jing-Rong Cui*   

  1. The State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100083, China
  • Received:2007-10-16 Revised:2008-01-10 Online:2008-03-15 Published:2008-03-15
  • Contact: Jing-Rong Cui*

摘要:

异臭椿类三萜具有很强的抗肿瘤及抗病毒等生理活性而备受人们关注。Jaspolide B是一种新发现的来源于海绵(Jaspis sp.)的异臭椿类三萜化合物, 本文将检测其对人早幼粒细胞白血病(HL-60)细胞的抗增殖作用, 并探讨其可能的作用机制。采用MTT法检测Jaspolide BHL-60细胞的抗增殖活性; 应用流式细胞术测定Jaspolide BHL-60细胞的周期阻滞与诱导凋亡作用; 并以免疫印迹和酶活力测定实验考察Jaspolide B 诱导HL-60细胞凋亡的机制。Jaspolide B HL-60细胞的抗增殖活性与紫杉醇相似, 均呈浓度依赖性, 处理48 h后的IC50值约为0.61 μmol/L; Jaspolide B 可浓度及时间依赖性地阻断HL-60细胞于G2/M; 并可增强Caspase-3活性、裂解PARP蛋白, 诱导HL-60细胞凋亡。因此, Jaspolide B可抑制HL-60细胞的增殖, 可能与其阻断肿瘤细胞于G2/M期及诱导细胞凋亡有关。

关键词: Jaspolide B, Jaspolide B, Jaspolide B, HL-60, HL-60, HL-60, 细胞周期, 细胞周期, 细胞周期, 凋亡, 凋亡, 凋亡

Abstract: The antiproliferative activity and underlying mechanisms of jaspolide B, an isomalabaricane-type triterpene, isolated from the sponge Jaspis sp., were investigated using human promyeloleukemic HL-60 cells. Jaspolide B arrested HL-60 cells in the G2/M phase of the cell cycle and induced apoptosis of HL-60 cells in a dose- and time-dependent manner. Moreover, the poly (ADP-ribose) polymerase (PARP) protein was cleaved by jaspolide in a dose- and time-dependent way. Jaspolide B with an IC50 value of 0.61 μmol/L was found to be comparable efficacy as that of paclitaxel (IC50: 0.78 μmol/L). These results implicate the potential of jaspolide B as a promising anticancer agent in chemotherapy of leukemia by arresting cell cycle progression at G2/M phase and triggering apoptosis.

Key words: Jaspolide B, Jaspolide B, HL-60, HL-60, Cell cycle, Cell cycle, Apoptosis, Apoptosis

中图分类号: 

Supporting: Foundation item: National High Technology Development Project (863 project) (Grants No. 2002AA217081 and 2002AA2Z343C), and NSFC (Grant No. 40176038).
*Corresponding author. Tel.: 86-10-82802467; fax: 86-10-82802724