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Inhibition of autophagy by 3-methyladenine potentiates sulforaphane-induced cell death of BE()-C human neuroblastoma cells

机译:3-甲基腺嘌呤抑制自噬增强了萝卜硫素诱导的BE()-C人神经母细胞瘤细胞的细胞死亡

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摘要

Sulforaphane (SFN) is an isothiocyanate present in cruciferous vegetables, which has been shown to exert an anti-cancer effect when tested in vitro and in vivo. The anti-cancer effects of SFN encompass induction of cytoprotective autophagy; therefore, the present study aimed to determine whether the chemopreventive activity of SFN may be potentiated by inhibition of autophagy. The present study provided detailed insight into the susceptibility of human neuroblastoma cells to treatment with synthetic SFN, in combination with an inhibitor of autophagy, 3-methyladenine (3-MA). The present study confirmed the suppression of the viability of the human neuroblastoma cell line BE(2)-C by SFN and reported the inhibition of DNA synthesis, as determined by a decrease in tritiated thymidine incorporation. Furthermore, the results verified the effectiveness of SFN in inducing apoptosis in the BE(2)-C cell line as demonstrated by caspase activation, increased protein expression levels of B-cell lymphoma 2-associated X protein and loss of mitochondrial membrane potential. Combined treatment of the cells with SFN with 3-MA proved to be effective in decreasing cell viability, through a mechanism that may proceed via the early induction of autophagy by SFN, followed by induction of apoptosis, as well as inhibition of autophagy by 3-MA.
机译:萝卜硫素(SFN)是十字花科蔬菜中存在的异硫氰酸盐,经体外和体内测试显示具有抗癌作用。 SFN的抗癌作用包括诱导细胞保护性自噬。因此,本研究旨在确定SFN的化学预防活性是否可以通过抑制自噬而增强。本研究提供了关于人类神经母细胞瘤细胞对合成SFN与自噬抑制剂3-甲基腺嘌呤(3-MA)结合治疗敏感性的详细见解。本研究证实了SFN抑制人神经母细胞瘤细胞系BE(2)-C的活力,并报告了DNA合成的抑制作用,这是由tri化胸苷掺入的减少确定的。此外,结果证实了SFN诱导BE(2)-C细胞系凋亡的有效性,如胱天蛋白酶激活,B细胞淋巴瘤2相关X蛋白的蛋白表达水平提高和线粒体膜电位丧失所证明。通过使用可能通过以下方式进行的机制,将SFN与3-MA联合处理可有效降低细胞生存力:一种机制可能是通过SFN早期诱导自噬,然后诱导细胞凋亡以及3-抑制自噬嘛。

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