基于天然产物的白血病细胞分化机制的化学生物学研究

Natural products-based chemical biology research on leukemic cell differentiation

天然产物由于具有结构多样性和新颖性,具有独特的生理活性和新的作用机制,因此是开展化学生物学研究的重要工具,同时也是创新药物和先导化合物的重要来源.最近,我们研究发现天然活性化合物腺花素能够在体内和体外诱导维甲酸敏感和耐药的急性粒细胞性白血病细胞发生分化,有效延长白血病小鼠生存时间.在此基础上,以腺花素为分子探针,"垂钓"其潜在的靶分子,结果发现腺花素特异性靶向过氧化还原酶(Peroxiredoxin)Ⅰ//Ⅱ蛋白,导致H2O2的积聚,H2O2作为第二信使可诱导白血病细胞分化的信号通路.本文对这些工作做了论述和展望.

Natural products are structurally diverse and novel,and they often possess unique biological activities.Therefore,natural compounds can serve as an important tool for chemical biology research and a great resource of innovative drugs and lead compounds.Based on the discovery that natural compound adenanthin induces differentiation of ATRA-sensitive and resistant acute promyelocytic leukemia（APL） cells in vivo and in vitro as well as prolongs the survival of APL leukemic mice.Recently we apply adenanthin as a chemical probe to identify its potential targets by cell extract-based pull-down assay and find that the adenanthin specifically targets peroxiredoxin Ⅰ//Ⅱ proteins and thus induces H2O2 accumulation,and the signal axsis involved in adenanthin-induced differentiation is explored as well.This minireview attempts to summarize these results and give prospect to its future development.