Biozentrum, Martin-Luther-Universität Halle-Wittenberg, Halle, Germany.
Invest New Drugs. 2011 Apr;29(2):266-72. doi: 10.1007/s10637-009-9358-x. Epub 2009 Dec 4.
In the present investigation the antiproliferative activity of thirteen derivatives of betulinic acid and betulin was tested against five different tumor cell lines. The toxicity against normal human fibroblasts (WWO70327) and the mode of cell death on HT-29 (colon cancer) as well as caspase activity induced by the most active compounds, 9 (3-O-chloroacetylbetulinic acid) and 15 (28-O-chloroacetylbetulin) were determined. Investigated derivatives exerted a dose dependent antiproliferative action at micromolar concentrations toward target tumor cell lines. Treatment of HT-29 cells for 24 h with 9 and 15 induced apoptosis, as observed by dye exclusion test (trypan blue) and confirmed by the appearance of a typical ladder pattern in the DNA fragmentation assay.
在本研究中，测试了 13 种白桦脂酸和白桦脂的衍生物对 5 种不同肿瘤细胞系的抗增殖活性。测定了它们对正常人类成纤维细胞（WWO70327）的毒性和对 HT-29（结肠癌）的细胞死亡方式，以及最活性化合物 9（3-O-氯乙酰基白桦脂酸）和 15（28-O-氯乙酰基白桦脂酸）诱导的半胱天冬酶活性。研究的衍生物在微摩尔浓度下对靶肿瘤细胞系表现出剂量依赖性的抗增殖作用。用 9 和 15 处理 HT-29 细胞 24 小时可诱导细胞凋亡，通过染料排除试验（台盼蓝）观察到，并用 DNA 片段化试验中出现典型的梯状模式证实。
