Baicalein induces human osteosarcoma cell line MG-63 apoptosis via ROS-induced BNIP3 expression

Baicalein induces human osteosarcoma cell line MG-63 apoptosis via ROS-induced BNIP3 expression
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黄芩素通过 ROS 诱导的 BNIP3 表达诱导人骨肉瘤细胞系 MG-63 凋亡。

DOI:
10.1007/s13277-015-3122-y
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发表时间:
2015-06-01
期刊:
影响因子:
--
通讯作者:
Huang, Jia
Huang, Jia
中科院分区:
其他
文献类型:
--
作者:
Ye, Fangfan;Wang, Honghan;Huang, Jia

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黄芩素是黄芩中的一种黄酮类化合物,是黄芩的有效成分之一。其抗肿瘤作用已引起世界各国的广泛关注。其主要功能之一是诱导肿瘤细胞凋亡,但其抗肿瘤机制目前尚不清楚。在本研究中,我们发现黄芩素增加MG-63细胞死亡率呈剂量依赖性。同时,黄芩苷通过诱导细胞内活性氧(ROS)的产生来激活细胞凋亡,而活性氧清除剂N-乙酰半胱氨酸(NAC)、谷胱甘肽(GSH)和超氧化物歧化酶(SOD)明显抑制细胞内活性氧的产生,从而减弱黄芩苷诱导的细胞凋亡。黄芩素还可诱导细胞凋亡前的线粒体断裂。这种形态学改变伴随着蛋白质BNIP 3以及Mul 1和Drp 1表达的增加。此外,我们发现抑制BNIP 3表达可以抑制黄芩素处理的细胞凋亡。综上所述,我们的研究结果提供了一种机制,即细胞凋亡和ROS诱导的BNIP 3表达与bacalein治疗MG-63细胞的证据,并表明黄芩素具有良好的潜力,作为一种抗骨肉瘤药物。
Baicalein, a flavonoid compound, is one of the active constituents of the root of Scutellariae Radix. Its antitumor effects have attracted widespread attention worldwide. One of its major functions is to induce the apoptosis of tumor cells, but the antitumor mechanism is currently unclear. In the present study, we found that baicalein increased MG-63 cell mortality in a dose-dependent manner. Meanwhile, baicalein activated apoptosis through induced intracellular reactive oxygen species (ROS) generation, and that ROS scavenger N-acetyl-cysteine (NAC), glutathione (GSH), and superoxide dismutase (SOD) apparently inhibited intracellular ROS production, consequently attenuating the baicalein-induced apoptosis. Baicalein also induce the mitochondrial fragmentation which precedes the cell apoptosis. This morphological alteration is accompanied by an increase in the expression of the protein BNIP3 as well as Mul1 and Drp1. Furthermore, we show that the inhibition of BNIP3 expression can inhibit cell apoptosis by baicalein treatment. Taken together, our results bring the evidence of a mechanism that links apoptosis and ROS-induced BNIP3 expression in MG-63 cells with bacalein treatment and suggest that baicalein has a good potential as an anti-osteosarcoma drug.