Cao Yu, Wang Fang, Liu Hong-Yan, Fu Zhao-Di, Han Rui
Department of Pharmacology, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, China.
J Asian Nat Prod Res. 2005 Aug;7(4):633-41. doi: 10.1080/1028602032000169523.
Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a naturally occurring phytoalexin found in grapes and wine, and has been reported to exert a variety of important pharmacological effects. We have investigated the activity of resveratrol on proliferation and differentiation of the acute promyelocytic leukemia cell line NB4. The growth inhibitory properties of resveratrol appear to be due to its induction of apoptotic cell death, as determined by morphological changes, DNA fragmentation, increased proportion of the subdiploid cell population and decreased mitochondrial transmembrane potential (Deltapsi(m)). Colorimetric assay for activity of caspase-3 showed an obvious increase in caspase-3 activity in cells after treatment with resveratrol. However, the expression levels of protein Bcl-2 and Bax show no significant change in response to resveratrol treatment. These results suggest that apoptosis of NB4 cells induced by resveratrol requires caspase-3 activation and is related to the mitochondrial transmembrane potential. The combination of resveratrol and all-tran-retinoic acid (ATRA) induced 100% of the NB4 cells to become NBT-positive, whereas only a small part of cells became positive for NBT after a similar exposure to either resveratrol or ATRA alone. Thus, resveratrol may be useful in treating acute promyelocytic leukemia.
白藜芦醇（3,5,4'-三羟基反式芪）是一种天然存在的植物抗毒素，存在于葡萄和葡萄酒中，据报道具有多种重要的药理作用。我们研究了白藜芦醇对急性早幼粒细胞白血病细胞系NB4增殖和分化的活性。白藜芦醇的生长抑制特性似乎是由于其诱导凋亡性细胞死亡，这通过形态学变化、DNA片段化、亚二倍体细胞群体比例增加以及线粒体跨膜电位（Δψm）降低来确定。用比色法检测caspase-3活性显示，白藜芦醇处理后的细胞中caspase-3活性明显增加。然而，蛋白Bcl-2和Bax的表达水平在白藜芦醇处理后没有显著变化。这些结果表明，白藜芦醇诱导的NB4细胞凋亡需要caspase-3激活，并且与线粒体跨膜电位有关。白藜芦醇和全反式维甲酸（ATRA）联合使用可使100%的NB4细胞变为NBT阳性，而单独用白藜芦醇或ATRA进行类似处理后只有一小部分细胞变为NBT阳性。因此，白藜芦醇可能对治疗急性早幼粒细胞白血病有用。
