Lycorine Induces Mitochondria-Dependent Apoptosis in Hepatoblastoma HepG2 Cells Through ROCK1 Activation
Lycorine Induces Mitochondria-Dependent Apoptosis in Hepatoblastoma HepG2 Cells Through ROCK1 Activation
复制标题
Lycorine 通过 ROCK1 激活诱导肝母细胞瘤 HepG2 细胞线粒体依赖性细胞凋亡
DOI：
10.3389/fphar.2019.00651
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发表时间：
2019-06-06
影响因子：
5.6
通讯作者：
Zhang, Rong
中科院分区：
文献类型：
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作者：
Liu, Wu-yi;Tang, Qin;Zhang, Rong
石蒜碱是一种天然存在的化合物，从Amaryllidaceae植物家族中提取，据报道，石蒜碱对各种类型的癌细胞都有抗肿瘤活性。在本研究中，我们研究了石蒜碱诱导肝母细胞瘤HepG2细胞凋亡的分子机制。我们发现，石松碱诱导HepG2细胞线粒体依赖性凋亡，并伴有线粒体通透性过渡孔（mPTP）打开、线粒体膜电位（MMP）丧失、三磷酸腺苷（ATP）耗损、Ca2+和细胞色素c （Cyto c）释放以及半胱天冬酶激活。此外，我们还发现Rho相关的含有蛋白激酶1 （ROCK1）的卷曲线圈的切割/激活在石蒜碱诱导的线粒体凋亡中起关键作用。此外，使用ROCK抑制剂Y-27632，我们发现与Y-27632共处理可减轻石蒜碱诱导的线粒体损伤和细胞凋亡。同时，一项体内研究表明，石蒜碱在HepG2异种移植小鼠模型中抑制肿瘤生长并诱导细胞凋亡，这与ROCK1激活有关。综上所述，这些发现提示石蒜碱通过激活HepG2细胞的ROCK1诱导线粒体依赖性细胞凋亡，这可能是石蒜碱具有抗癌作用的理论基础。
Lycorine, a naturally occurring compound extracted from the Amaryllidaceae plant family, has been reported to exhibit antitumor activity in various cancer cell types. In the present study, we investigated the molecular mechanisms underlying lycorine-induced apoptosis in hepatoblastoma HepG2 cells. We found that lycorine induced mitochondria-dependent apoptosis in HepG2 cells accompanied by mitochondrial permeability transition pore (mPTP) opening, mitochondrial membrane potential (MMP) loss, adenosine triphosphate (ATP) depletion, Ca2+ and cytochrome c (Cyto C) release, as well as caspase activation. Furthermore, we found Rho associated coiled-coil containing protein kinase 1 (ROCK1) cleavage/activation played a critical role in lycorine-induced mitochondrial apoptosis. In addition, the ROCK inhibitor Y-27632 was employed, and we found that co-treatment with Y-27632 attenuated lycorine-induced mitochondrial injury and cell apoptosis. Meanwhile, an in vivo study revealed that lycorine inhibited tumor growth and induced apoptosis in a HepG2 xenograft mouse model in association with ROCK1 activation. Taken together, all these findings suggested that lycorine induced mitochondria-dependent apoptosis through ROCK1 activation in HepG2 cells, and this may be a theoretical basis for lycorine's anticancer effects.