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首页> 外文期刊>Apoptosis >The microtubule depolymerizing agent naphthazarin induces both apoptosis and autophagy in A549 lung cancer cells
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The microtubule depolymerizing agent naphthazarin induces both apoptosis and autophagy in A549 lung cancer cells

机译：微管解聚剂萘他林可诱导A549肺癌细胞凋亡和自噬

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摘要

Naphthazarin (DHNQ, 5,8-dihydroxy-l,4-naphthoquinone) is a naturally available 1,4-naphthoquinone derivatives. In this study, we focused on elucidating the cytotoxic mechanism of naphthazarin in A549 non-small cell lung carcinoma cells. Naphthazarin reduced the A549 cell viability considerably with an IC50 of 16.4 ± 1.6 μM. Naphthazarin induced cell death in a dose- and time-dependent manner by activating apoptosis and autophagy pathways. Specifically, we found naphthazarin inhibited the PI3K/Akt cell survival signalling pathway, measured by p53 and caspase-3 activation, and PARP cleavage. It also resulted in an increase in the ratio of Bax/Bcl2 protein levels, indicating activation of the mitochondrial apoptotic pathway. Similarly naphthazarin triggered LC3II expression and induced autophagic flux in A549 cells. We demonstrated further that naphthazarin is a microtubule inhibitor in cell-free system and in A549 cells. Naphthazarin treatment depolymerized interphase microtubules and disorganised spindle microtubules and the majority of cells arrested at the G2/M transition. Together, these data suggest that naphthazarin, a microtubule depolymerizer which activates dual cell death machineries, could be a potential novel chemotherapeutic agent.
机译：萘达沙林（DHNQ，5，8-二羟基-1，4-萘醌）是天然可获得的1，4-萘醌衍生物。在这项研究中，我们集中于阐明萘他林在A549非小细胞肺癌细胞中的细胞毒性机制。萘达那林大大降低了A549细胞的活力，IC 50 的IC值为16.4±1.6μM。萘达沙林通过激活细胞凋亡和自噬途径，以剂量和时间依赖性的方式诱导细胞死亡。具体而言，我们发现萘普沙林抑制了PI3K / Akt细胞存活信号转导途径，该途径通过p53和caspase-3激活以及PARP裂解来测量。这也导致Bax / Bcl2蛋白水平比率的增加，表明线粒体凋亡途径的激活。类似地，萘达那林在A549细胞中触发LC3II表达并诱导自噬通量。我们进一步证明了萘他林是无细胞系统和A549细胞中的微管抑制剂。萘达那林处理使相间微管解聚，纺锤体微管混乱，大部分细胞在G 2 / M转变中停滞。总而言之，这些数据表明，萘达那林（一种激活双细胞死亡机制的微管解聚剂）可能是潜在的新型化学治疗剂。

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