Gong Xian-Feng, Wang Min-Wei, Tashiro Shin-Ichi, Onodera Satoshi, Ikejima Takashi
China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang 110016, China.
Arch Pharm Res. 2005 Jan;28(1):68-72. doi: 10.1007/BF02975138.
Pseudolaric acid B is a major compound found in the bark of Pseudolarix kaempferi Gordon. In our study, pseudolaric acid B inhibited growth of human melanoma cells, A375-S2 in a time- and dose-dependent manner. A375-S2 cells treated with pseudolaric acid B showed typical characteristics of apoptosis including morphologic changes, DNA fragmentation, sub-diploid peak in flow cytometry, cleavage of poly-ADP ribose polymerase (PARP) and degradation of inhibitor of caspase-activated DNase (ICAD). P53 protein expression was upregulated while cells were arrested at the G2/M phase of the cell cycle. There was a decrease in the expression of anti-apoptotic Bcl-2 and Bcl-xL proteins, whereas pro-apoptotic Bax was increased. The two classical caspase substrates, PARP and ICAD, were both decreased in a time-dependent manner, indicating the activation of downstream caspases.
土槿皮酸B是金钱松（Pseudolarix kaempferi Gordon）树皮中发现的一种主要化合物。在我们的研究中，土槿皮酸B以时间和剂量依赖性方式抑制人黑色素瘤细胞A375-S2的生长。用土槿皮酸B处理的A375-S2细胞表现出典型的凋亡特征，包括形态学变化、DNA片段化、流式细胞术中的亚二倍体峰、聚ADP核糖聚合酶（PARP）的切割以及半胱天冬酶激活的DNA酶抑制剂（ICAD）的降解。当细胞停滞在细胞周期的G2/M期时，P53蛋白表达上调。抗凋亡蛋白Bcl-2和Bcl-xL的表达降低，而促凋亡蛋白Bax增加。两种经典的半胱天冬酶底物PARP和ICAD均呈时间依赖性降低，表明下游半胱天冬酶被激活。
