Xu Mei-Ying, Kim Yeong Shik
Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
Food Chem Toxicol. 2014 Dec;74:311-9. doi: 10.1016/j.fct.2014.10.023.
Glycyrol is a coumestan isolated from Glycyrrhiza uralensis and synthesized to use. In this study, the antitumor activity and the underlying mechanism of glycyrol were evaluated in vitro and in vivo. It was shown that glycyrol induced cell death associated with apoptosis and autophagy as evidenced by morphological changes in AGS and HCT 116 cells. The apoptosis-inducing effect was characterized by increase in ratio of sub-G1 phase, poly (ADP-ribose) polymerase-1 (PARP-1) cleavage and caspase-3 activation. Mechanistic studies showed that glycyrol induced G0/G1 phase cell cycle arrest as indicated by increase in p21. Furthermore, c-Jun N-terminal kinase (JNK)/p38 mitogen-activated protein kinases (MAPKs) activation induced caspase-dependent apoptosis accompanied by adenosine monophosphate-activated protein kinase (AMPK) activation. Defective autophagy was triggered, which stopped the autophagic flux by the slowing of lysosomal degradation. In addition, glycyrol suppressed tumor growth in a nude mouse tumor xenograft model bearing HCT 116 cells. Taken together, glycyrol is demonstrated to have antitumor activity, and might potentially serve as potential candidate for cancer therapy.
甘草醇是从甘草中分离出来并经合成后用于研究的一种香豆雌酚。在本研究中，对甘草醇的体外和体内抗肿瘤活性及其潜在机制进行了评估。结果表明，甘草醇诱导细胞死亡与凋亡和自噬相关，AGS和HCT 116细胞的形态变化证明了这一点。凋亡诱导作用的特征是亚G1期比例增加、聚（ADP - 核糖）聚合酶 - 1（PARP - 1）裂解和半胱天冬酶 - 3激活。机制研究表明，甘草醇诱导G0/G1期细胞周期停滞，p21增加表明了这一点。此外，c - Jun氨基末端激酶（JNK）/p38丝裂原活化蛋白激酶（MAPK）激活诱导半胱天冬酶依赖性凋亡，并伴有腺苷单磷酸活化蛋白激酶（AMPK）激活。引发了自噬缺陷，通过溶酶体降解减缓阻止了自噬流。此外，甘草醇在携带HCT 116细胞的裸鼠肿瘤异种移植模型中抑制了肿瘤生长。综上所述，甘草醇被证明具有抗肿瘤活性，可能潜在地作为癌症治疗的候选药物。
