College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea.
Int J Mol Sci. 2018 Sep 10;19(9):2681. doi: 10.3390/ijms19092681.
Although Moracin D derived from was known to have anti-inflammatory and antioxidant activities, the underlying antitumor mechanism of Moracin D has not been unveiled thus far. Thus, in the recent study, the apoptotic mechanism of Moracin D was elucidated in breast cancer cells. Herein, Moracin D exerted significant cytotoxicity in MDA-MB-231 and MCF-7 cells. Furthermore, Moracin D increased sub G1 population; cleaved poly (Adenosine diphosphate (ADP-ribose)) polymerase (PARP); activated cysteine aspartyl-specific protease 3 (caspase 3); and attenuated the expression of c-Myc, cyclin D1, B-cell lymphoma 2 (Bcl-2), and X-linked inhibitor of apoptosis protein (XIAP) in MDA-MB231 cells. Of note, Moracin D reduced expression of Forkhead box M1 (FOXM1), β-catenin, Wnt3a, and upregulated glycogen synthase kinase 3 beta (GSK3β) on Tyr216 along with disturbed binding of FOXM1 with β-catenin in MDA-MB-231 cells. Conversely, GSK3β inhibitor SB216763 reversed the apoptotic ability of Moracin D to reduce expression of FOXM1, β-catenin, pro-caspase3, and pro-PARP in MDA-MB-231 cells. Overall, these findings provide novel insight that Moracin D inhibits proliferation and induces apoptosis via suppression of Wnt3a/FOXM1/β-catenin signaling and activation of caspases and GSK3β.
虽然从 中提取的 Moracin D 已知具有抗炎和抗氧化活性，但迄今为止，Moracin D 的抗肿瘤机制尚未被揭示。因此，在最近的研究中，阐明了 Moracin D 在乳腺癌细胞中的凋亡机制。在这里，Moracin D 在 MDA-MB-231 和 MCF-7 细胞中表现出显著的细胞毒性。此外，Moracin D 增加了 sub G1 群体；切割多聚（二磷酸腺苷（ADP-核糖））聚合酶（PARP）；激活半胱氨酸天冬氨酸特异性蛋白酶 3（caspase 3）；并降低 MDA-MB231 细胞中 c-Myc、细胞周期蛋白 D1、B 细胞淋巴瘤 2 (Bcl-2) 和 X 连锁凋亡蛋白抑制剂（XIAP）的表达。值得注意的是，Moracin D 降低了 Forkhead box M1 (FOXM1)、β-连环蛋白、Wnt3a 和糖原合酶激酶 3β (GSK3β) 在 Tyr216 上的表达，同时扰乱了 FOXM1 与 MDA-MB-231 细胞中β-连环蛋白的结合。相反，GSK3β 抑制剂 SB216763 逆转了 Moracin D 诱导 MDA-MB-231 细胞凋亡的能力，降低了 FOXM1、β-连环蛋白、pro-caspase3 和 pro-PARP 的表达。总的来说，这些发现提供了新的见解，即 Moracin D 通过抑制 Wnt3a/FOXM1/β-连环蛋白信号通路和激活 caspase 和 GSK3β 来抑制增殖并诱导凋亡。
