Dimas K, Kokkinopoulos D, Demetzos C, Vaos B, Marselos M, Malamas M, Tzavaras T
Department of Immunology, Hellenic Anticancer Institute, Athens, Greece.
Leuk Res. 1999 Mar;23(3):217-34. doi: 10.1016/s0145-2126(98)00134-9.
Sclareol, a labdane-type diterpene, was tested for cytotoxic effect against a panel of established human leukemic cell lines. The compound showed an IC50 lower than 20 microg/ml in most cell lines tested, while it was higher for resting peripheral blood mononuclear leukocytes (PBML). Furthermore, the compound was tested for cytostatic activity against four of the leukemic cell lines used. At a concentration of 20 microg/ml the compound showed a significant cytostatic effect as soon as 4 h after continuous incubation against two from B and two from T lineage cell lines. The morphology and the kind of death induced from sclareol in three cell lines, was also investigated. The effect of sclareol on the cell cycle progression of two cell lines, using flow cytometry, was examined. The results show that sclareol kills cell lines, through the process of apoptosis. The appearance of the apoptotic signs is time and dose dependent. From the flow cytometry experiments, a delay of the cell population on G0/1 seems to take place. This is the first report, that a labdane type diterpene kills tumor cells via a phase specific mechanism which induces apoptosis.
硬尾醇，一种半日花烷型二萜，针对一系列已建立的人类白血病细胞系进行了细胞毒性测试。在大多数测试的细胞系中，该化合物的半数抑制浓度（IC50）低于20微克/毫升，而对于静息外周血单个核白细胞（PBML）则较高。此外，还针对所使用的四种白血病细胞系测试了该化合物的细胞生长抑制活性。在20微克/毫升的浓度下，连续孵育4小时后，该化合物对两种B系和两种T系细胞系均显示出显著的细胞生长抑制作用。还研究了硬尾醇在三种细胞系中诱导的细胞死亡形态和类型。使用流式细胞术检测了硬尾醇对两种细胞系细胞周期进程的影响。结果表明，硬尾醇通过凋亡过程杀死细胞系。凋亡迹象的出现具有时间和剂量依赖性。流式细胞术实验表明，细胞群体在G0/1期似乎出现延迟。这是首次报道一种半日花烷型二萜通过诱导凋亡的阶段特异性机制杀死肿瘤细胞。
