Erianin induces G2/M-phase arrest, apoptosis, and autophagy via the ROS/JNK signaling pathway in human osteosarcoma cells in vitro and in vivo.
Erianin induces G2/M-phase arrest, apoptosis, and autophagy via the ROS/JNK signaling pathway in human osteosarcoma cells in vitro and in vivo.
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毛兰素通过 ROS/JNK 信号通路在体外和体内诱导人骨肉瘤细胞 G2/M 期阻滞、细胞凋亡和自噬
DOI：
10.1038/cddis.2016.138
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发表时间：
2016-06-02
影响因子：
9
通讯作者：
中科院分区：
文献类型：
--
作者：
毛兰素是从鼓槌石斛（Dendrobium chrysotoxum）中提取的一种天然产物，对肝癌、黑色素瘤、早幼粒细胞白血病等多种恶性肿瘤具有潜在的抗肿瘤活性。本研究旨在探讨毛兰素对骨肉瘤（OS）的体内外作用，并进一步阐明其分子机制。在这项研究中，我们发现毛兰素有效地抑制各种OS细胞系中的细胞活力。毛兰素诱导OS细胞发生G2/M期阻滞、凋亡和自噬。进一步的研究表明毛兰素诱导的细胞凋亡和自噬是由活性氧（ROS）引起的，而活性氧清除剂N-乙酰半胱氨酸（NAC）可以减弱它们。此外，我们发现毛兰素诱导c-Jun N-末端激酶（JNK）信号通路的激活，这也被NAC阻断。JNK特异性抑制剂SP 600125下调JNK的表达可减轻毛兰素诱导的细胞凋亡和自噬。最后，毛兰素在体内显着降低的生长几乎没有器官相关的毒性。总之，毛兰素诱导细胞周期G2/M期阻滞，凋亡，并通过ROS/JNK信号通路在人类OS自噬。根据这些结果，毛兰素可能是一个有前途的代理抗OS的抗癌治疗。
Erianin, a natural product derived from Dendrobium chrysotoxum, has exhibited potential antitumor activity in various malignancies, including hepatocarcinoma, melanoma, and promyelocytic leukemia. Here we explored the effects of erianin on osteosarcoma (OS) in vitro and in vivo and further elucidated the underlying molecule mechanisms. In this study, we found that erianin potently suppressed cell viability in various OS cell lines. Treatment with erianin induced G2/M-phase arrest, apoptosis, and autophagy in OS cells. Further studies showed that erianin-induced apoptosis and autophagy was attributed to reactive oxygen species (ROS), as N-acetyl cysteine (NAC), an ROS scavenger, attenuated them. Moreover, we found that erianin induced activation of c-Jun N-terminal kinase (JNK) signal pathway, which was also blocked by NAC. Downregulation of JNK by its specific inhibitor SP600125 could attenuate apoptosis and autophagy induced by erianin. Finally, erianin in vivo markedly reduced the growth with little organ-related toxicity. In conclusion, erianin induced cell cycle G2/M-phase arrest, apoptosis, and autophagy via the ROS/JNK signaling pathway in human OS. In light of these results, erianin may be a promising agent for anticancer therapy against OS.
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