Yi Zongchun, Wang Zhao, Li Haixia, Liu Mingjie
Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing 100084, China.
Toxicol Lett. 2004 Mar 1;147(2):109-19. doi: 10.1016/j.toxlet.2003.12.008.
Tellimagrandin I is a hydrolysable tannin compound widely present in plants. In this study, the effect of tellimagrandin I on chemically induced erythroid and megakaryocytic differentiation was investigated using K562 cells as differentiation model. It was found that tellimagrandin I not only inhibited the hemoglobin synthesis in butyric acid (BA)- and hemin-induced K562 cells with IC50 of 3 and 40microM, respectively, but also inhibited other erythroid differentiation marker including acetylcholinesterase (AChE) and glycophorin A (GPA) in BA-induced K562 cells. Tellimagrandin I also inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced expression of CD61 protein, a megakaryocytic marker. RT-PCR analysis showed that tellimagrandin I decreased the expression of erythroid genes (gamma-globin and porphobilinogen deaminase (PBGD)) and related transcription factors (GATA-1 and NF-E2) in BA-induced K562 cells, whereas tellimagrandin I induced the overexpresison of GATA-2 transcription factor that played negative regulation on erythroid differentiation. These results indicated that tellimagrandin I had inhibitory effects on erythroid and megakaryocytic differentiation, which suggested that tannins like tellimagrandin I might influence the anti-tumor efficiency of some drugs and the hematopoiesis processes.
tellimagrandin I是一种广泛存在于植物中的可水解单宁化合物。在本研究中,以K562细胞作为分化模型,研究了tellimagrandin I对化学诱导的红系和巨核系分化的影响。结果发现,tellimagrandin I不仅抑制丁酸(BA)和血红素诱导的K562细胞中的血红蛋白合成,IC50分别为3和40μM,而且还抑制BA诱导的K562细胞中的其他红系分化标志物,包括乙酰胆碱酯酶(AChE)和血型糖蛋白A(GPA)。tellimagrandin I还抑制12-O-十四烷酰佛波醇-13-乙酸酯(TPA)诱导的巨核细胞标志物CD61蛋白的表达。RT-PCR分析表明,tellimagrandin I降低了BA诱导的K562细胞中红系基因(γ-珠蛋白和胆色素原脱氨酶(PBGD))和相关转录因子(GATA-1和NF-E2)的表达,而tellimagrandin I诱导了对红系分化起负调控作用的GATA-2转录因子的过表达。这些结果表明,tellimagrandin I对红系和巨核系分化具有抑制作用,这表明像tellimagrandin I这样的单宁可能会影响某些药物的抗肿瘤效率和造血过程。