摘要
柴胡提取物诱导人类白血病细胞HL-60的细胞凋亡从而抑制其细胞生长。为了研究该过程的作用机理,我们研究了丝裂原活化蛋白激酶(MAPKs),包括胞外信号调节激酶(ERK1/2),c-jun氨基末端蛋白激酶(JNK)和p38丝裂原活化蛋白激酶(MAPK),在该过程中的磷酸化特征与动态变化。结果表明,柴胡提取物显著的增加了p38丝裂原活化蛋白激酶和胞外信号调节激酶(ERK1/2)的磷酸化作用,其增加值在测试范围内与测试剂量和作用时间成正相关,但在柴胡提取物诱导人类白血病细胞HL-60的细胞凋亡过程中,没有发现对氨基末端蛋白激酶(JNK)表现出磷酸化活性。柴胡提取物诱导白血病HL-60的细胞凋亡部分归结于对p38丝裂原活化蛋白激酶的上调节作用,这种上调节作用能够受到p38 MAPK特异性的抑制剂SB203580的部分逆转,而MEK的抑制剂U0126则对柴胡提取物诱导HL-60细胞凋亡过程中的胞外信号调节激酶(ERK1/2)的磷酸化具有显著的协同效应。这是首次报道柴胡提取物在诱导人白血病细胞HL-60细胞凋亡过程中参与p38丝裂原活化蛋白激酶的磷酸化,同时柴胡提取物作为胞外信号调节激酶(ERK1/2)抑制剂的协同作用物具有相应的药物学功能。
Abstract：Treatment of human leukemia HL-60 cells with the Bupleurum chinensis extract inhibits cell growth and induces apoptosis. In order to study the acting mechanism of the effect, we examined the role of mitogen-activated protein kinases （MAPKs） including extracellular signal-related kinase （ERK1/2）, c-jun N terminal protein kinase （JNK）, and p38 MAPK in B. chinensis extract-induced growth inhibition and apoptosis in human leukemia HL-60 ceils. Among the three kinases examincd,B, chinensis extract specifically increased the phosphorylation of both p38 MAPK and ERK1/2 in a doseand time-dependent manner, but did not inhibited phosphorylation activity of JNK. The result provided mecha- nistic information that Bupleurum extract exerted the proapoptotic effects on HL-60 ceils partially by upregulating p38 MAPK activity ,whereas the JNK was not activated during the extract-induced apoptosis. Treatment using specific p38 in- hibitor SB203580 partially reversed the effect of B. chinensis extract on the cell growth inhibition and apoptosis, whiletreatment with MEK inhibitor U0126 dramatically synergized the effect of the extract. This is the first report that p38 MAPK activation in HL-60 ceils is involved in the ceil death and apoptosis induced by the B. chinensis extract, while ex- tract-induced ERK1/2 phosphorylation acted as a survival factor and specific inhibitors of ERKI/2 pathway may serveas sensitizers towards B. chinensis extract-mediated apoptosis.
出处
《天然产物研究与开发》
CAS
CSCD
北大核心
2013年第2期177-184,233,共9页
Natural Product Research and Development
基金
partially funded by the State Principaland Basic Research and Development Program of the Ministry of Sciencesand Technology of China(2010CB833801)
Guangdong Provincial Science and Technology Projects(2012B091100276)
