Huang Hsin-Lien, Hsieh Ming-Ju, Chien Ming-Hsien, Chen Hui-Yu, Yang Shun-Fa, Hsiao Pei-Ching
Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; Cancer Research Center, Changhua Christian Hospital, Changhua, Taiwan; School of Optometry, Chung Shan Medical University, Taichung, Taiwan.
PLoS One. 2014 Jun 5;9(6):e98943. doi: 10.1371/journal.pone.0098943. eCollection 2014.
Glabridin, a prenylated isoflavonoid of G. glabra L. roots, has been associated with a wide range of biological properties such as regulation of energy metabolism, estrogenic, neuroprotective, anti-osteoporotic, and skin-whitening in previous studies. However, the effect of glabridin on tumor cells metastasis has not been clearly clarified. Here, the molecular mechanism by which glabridin anticancer effects in human promyelocytic leukemia cells was investigated.
The results showed that glabridin significantly inhibited cell proliferation of four AML cell lines (HL-60, MV4-11, U937, and THP-1). Furthermore, glabridin induced apoptosis of HL-60 cells through caspases-3, -8, and -9 activations and PARP cleavage in dose- and time-dependent manner. Moreover, western blot analysis also showed that glabridin increase phosphorylation of ERK1/2, p38 MAPK and JNK1/2 in dose- and time-dependent manner. Inhibition of p38 MAPK and JNK1/2 by specific inhibitors significantly abolished the glabridin-induced activation of the caspase-3, -8 and -9.
Taken together, our results suggest that glabridin induced HL-60 cell apoptosis through p38 MAPK and JNK1/2 pathways and could serve as a potential additional chemotherapeutic agent for treating AML.
光甘草定是光果甘草根中的一种异戊烯基化异黄酮，在先前的研究中已发现其具有多种生物学特性，如调节能量代谢、雌激素样作用、神经保护、抗骨质疏松和美白皮肤等。然而，光甘草定对肿瘤细胞转移的影响尚未明确阐明。在此，我们研究了光甘草定在人早幼粒细胞白血病细胞中发挥抗癌作用的分子机制。
结果显示，光甘草定显著抑制四种急性髓系白血病细胞系（HL-60、MV4-11、U937和THP-1）的细胞增殖。此外，光甘草定通过激活半胱天冬酶-3、-8和-9以及切割聚（ADP-核糖）聚合酶，以剂量和时间依赖性方式诱导HL-60细胞凋亡。而且，蛋白质印迹分析还表明，光甘草定以剂量和时间依赖性方式增加细胞外信号调节激酶1/2（ERK1/2）、p38丝裂原活化蛋白激酶（p38 MAPK）和应激活化蛋白激酶1/2（JNK1/2）的磷酸化。用特异性抑制剂抑制p38 MAPK和JNK1/2可显著消除光甘草定诱导的半胱天冬酶-3、-8和-9的激活。
综上所述，我们的结果表明光甘草定通过p38 MAPK和JNK1/2途径诱导HL-60细胞凋亡，可作为治疗急性髓系白血病的一种潜在的辅助化疗药物。
