Ankaflavin and Monascin Induce Apoptosis in Activated Hepatic Stellate Cells through Suppression of the Akt/NF-κB/p38 Signaling Pathway
Ankaflavin and Monascin Induce Apoptosis in Activated Hepatic Stellate Cells through Suppression of the Akt/NF-κB/p38 Signaling Pathway
复制标题
安卡黄素和单核球蛋白通过抑制Akt/NF-κB/p38信号通路诱导活化的肝星状细胞凋亡
DOI：
10.1021/acs.jafc.6b03700
复制
发表时间：
2016-12-14
影响因子：
6.1
通讯作者：
Pan, Tzu-Ming
中科院分区：
文献类型：
--
作者：
Cheng, Chih-Fu;Pan, Tzu-Ming
活化的肝星状细胞（HSC）增殖增加与肝纤维化和过量的细胞外基质（ECM）-蛋白产生相关。我们研究了红曲霉发酵的代谢产物，ankaflavin和monascin（15和30 μ M），对HSC-T6（活化的肝星状细胞系）中的Aid/核因子（NF）-κ B和p38丝裂原活化蛋白激酶（MAPK）信号通路的抑制作用。Ankaflavin和Monascin（30 μ M）诱导细胞凋亡并显著抑制细胞生长（细胞存活率：与对照细胞相比分别为80.2 +/- 5.43%和62.8 +/-8.20%; P < 0.05）。细胞凋亡和G1期阻滞（G1期百分比分别为76.1 +/- 2.85%和79.9 +/-1.80%，对照组为65.9 +/- 4.94%; P < 0.05）与p53和p21水平和caspase 3活性升高以及cydin D1和Bc 1 -2家族蛋白水平降低相关（P < 0.05，所有病例）。安卡黄素和红曲素的凋亡作用是HSC-T6特异性的，表明它们在治疗肝纤维化方面的潜力。
The increased proliferation of activated hepatic stellate cells (HSCs) is associated with hepatic fibrosis and excessive extracellular matrix (ECM)-protein production. We examined the inhibitory effects of the Monascus purpureusfermented metabolites, ankaflavin and monascin (15 and 30 mu M), on the Aid/nuclear factor (NF)-kappa B and p38 mitogen-activated protein kinase (MAPK) signaling pathways in HSC-T6 (activated hepatic stellate cell line). Ankaflavin and monascin (30 mu M) induced apoptosis and significantly inhibited cell growth (cell viabilities: 80.2 +/- 5.43% and 62.8 +/- 8.20%, respectively, versus control cells; P < 0.05). Apoptosis and G1 phase arrest (G1 phase percentages: 76.1 +/- 2.85% and 79.9 +/- 1.80%, respectively, versus control cells 65.9 +/- 4.94%; P < 0.05) correlated with increased p53 and p21 levels and caspase 3 activity and decreased cydin D1 and Bc1-2-family protein levels (P < 0.05, all cases). The apoptotic effects of ankaflavin and monascin were HSC-T6-specific, suggesting their potential in treating liver fibrosis.