Kong Dexin, Aoki Shunji, Sowa Yoshihiro, Sakai Toshiyuki, Kobayashi Motomasa
Graduate School of Pharmaceutical Sciences, Osaka University, Yamada-oka 1-6, Suita, Osaka 565-0871, Japan.
Mar Drugs. 2008;6(3):480-8. doi: 10.3390/md20080023. Epub 2008 Aug 26.
Smenospongine, a sesquiterpene aminoquinone isolated from the marine sponge Dactylospongia elegans, was previously reported by us to induce erythroid differentiation and G1 phase arrest of K562 chronic myelogenous leukemia cells. In this study, we investigated the effect of smenospongine on the cell cycles of other leukemia cells, including HL60 human acute promyelocytic leukemia cells and U937 human histiocytic lymphoma cells by flow cytometric analysis. Smenospongine induced apoptosis dose-dependently in HL60 and U937 cells. The smenospongine treatment increased expression of p21 and inhibited phosphorylation of Rb in K562 cells, suggesting the p21-Rb pathway play an important role in G1 arrest in K562 cells. However, the p21 promoter was not activated by the smenospongine treatment based on a luciferase assay using the transfected K562 cells. Smenospongine might induce p21 expression via another mechanism than transactivation of p21 promoter.
半海绵醌是从海洋海绵优雅指海绵(Dactylospongia elegans)中分离出的一种倍半萜氨基醌,我们之前报道过它能诱导K562慢性粒细胞白血病细胞的红系分化和G1期阻滞。在本研究中,我们通过流式细胞术分析研究了半海绵醌对其他白血病细胞周期的影响,这些细胞包括HL60人急性早幼粒细胞白血病细胞和U937人组织细胞淋巴瘤细胞。半海绵醌在HL60和U937细胞中剂量依赖性地诱导凋亡。半海绵醌处理增加了K562细胞中p21的表达并抑制了Rb的磷酸化,这表明p21-Rb途径在K562细胞的G1期阻滞中起重要作用。然而,基于使用转染的K562细胞的荧光素酶测定,半海绵醌处理并未激活p21启动子。半海绵醌可能通过不同于p21启动子反式激活的另一种机制诱导p21表达。