Jeju center, Korea Basic Science Institute (KBSI), Jeju 690-140, Republic of Korea.
Food Chem. 2012 Dec 1;135(3):2112-7. doi: 10.1016/j.foodchem.2012.05.067. Epub 2012 May 23.
The present study was designed to evaluate the molecular mechanisms of the action of acanthoic acid (ACAN) from Acanthopanax koreanum (Araliaceae) against HL-60 human promyelocytic leukaemia cells. ACAN reduced the proliferation of HL-60 cells in a dose- and time-dependent manner accompanied by the induction of apoptosis. Possible mechanisms of ACAN-induced apoptosis were also examined. The results showed that ACAN-induced the phosphorylation of members of the mitogen-activated protein kinase (MAPK) family, c-Jun N-terminal kinase (JNK), p38 MAPK (p38), and extracellular signal-regulated kinase (ERK). A specific p38 MAPK inhibitor (SB203580) significantly blocked ACAN-induced apoptosis and cell viability, whereas an ERK inhibitor (PD98059) and JNK inhibitor (SP600125) had no effect. Moreover, ACAN induced the cleavage of caspase-3 and poly-ADP-ribose polymerase (PARP), and decreased the level of Bcl-xL, but these effects were inhibited by SB203580 pre-treatment. These results strongly suggest that ACAN may have cancer chemopreventive and therapeutic potential, due to its ability to activate the p38 MAPK-mediated signalling pathways.
本研究旨在评估刺五加酸（ACAN）从刺五加（五加科）对 HL-60 人早幼粒细胞白血病细胞作用的分子机制。ACAN 以剂量和时间依赖的方式减少 HL-60 细胞的增殖，同时诱导细胞凋亡。还检查了 ACAN 诱导细胞凋亡的可能机制。结果表明，ACAN 诱导丝裂原活化蛋白激酶（MAPK）家族成员、c-Jun N-末端激酶（JNK）、p38 MAPK（p38）和细胞外信号调节激酶（ERK）的磷酸化。特异性 p38 MAPK 抑制剂（SB203580）显著阻断 ACAN 诱导的细胞凋亡和细胞活力，而 ERK 抑制剂（PD98059）和 JNK 抑制剂（SP600125）没有作用。此外，ACAN 诱导 caspase-3 和多聚（ADP-核糖）聚合酶（PARP）的裂解，并降低 Bcl-xL 的水平，但这些作用被 SB203580 预处理所抑制。这些结果强烈表明，ACAN 可能具有癌症化学预防和治疗潜力，因为它能够激活 p38 MAPK 介导的信号通路。
