Shikonin, a naphthoquinone compound, rapidly induces cell death of human myeloma cells via production of reactive oxygen species
Shikonin, a naphthoquinone compound, rapidly induces cell death of human myeloma cells via production of reactive oxygen species
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发表时间：
2014
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通讯作者：
Takahiro Kimura;T. Nakazato;M. Kizaki
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作者：
Takahiro Kimura;T. Nakazato;M. Kizaki
紫草素是从中草药紫草中提取的一种萘醌类化合物。已发现其具有多种生物活性，包括强烈的伤口愈合、抗菌、抗炎和抗肿瘤作用。最近，有报道称紫草素可诱导多种癌细胞死亡。然而，负责这些活动的机制仍不清楚。此外，还没有关于紫草素对多发性骨髓瘤细胞的影响的研究。在本研究中，我们研究了紫草素对人多发性骨髓瘤细胞增殖、细胞周期进程和细胞死亡机制的影响。紫草素通过诱导细胞凋亡，显著抑制多种骨髓瘤细胞系的生长。紫草素诱导的细胞死亡与线粒体跨膜电位(ΔΨm)的丧失、细胞质c的释放和Smac/DIABLO有关。在紫草素诱导的骨髓瘤细胞死亡过程中，细胞内氧物种(ROS)的产生增加。紫草素能显著抑制IL-6诱导的骨髓瘤细胞中STAT3的磷酸化。抗氧化剂NAC可减轻紫草素诱导的细胞死亡和抑制骨髓瘤细胞中STAT3的磷酸化。我们的结果表明，紫草素诱导骨髓瘤细胞死亡，这是通过抑制线粒体损伤和通过产生ROS来抑制IL-6/STAT通路而实现的。
Shikonin is a naphthoquinone derivative extracted from a traditional Chinese medical herb, Lithospermum erythrorhizon. It has been found to posses a variety of biological activities including strong wound healing, antibacterial, anti-inflammatory, and anti-tumor effects. Recently, it has been reported that shikonin induces cell death of various cancer cells. However, the mechanisms responsible for these activities remain unknown. In addition, no studies have addressed the effects of shikonin on multiple myeloma cells. In this study, we investigated the effects of shikonin on cell proliferation, cell cycle progression, and mechanism of apoptotic cell death in human multiple myeloma cells. Shikonin markedly suppressed the cellular growth of various myeloma cell lines via induction of apoptosis. Shikonin-induced cell death was in association with the loss of mitochondrial transmembrane potentials (ΔΨm), the release of cytocrome c and Smac/DIABLO. Elevation of intracellular oxygen species (ROS) production was shown during shikonin-induced cell death in myeloma cells. Shikonin markedly inhibited IL-6-induced phosphorylation of STAT3 in myeloma cells. The antioxidants, NAC, ameliorated shikonin-induced cell death and inhibition of STAT3 phosphorylation in myeloma cells. Our results indicate that shikonin induced cell death in myeloma cells, and that this was mediated through inhibition of mitochondrial damage and IL-6/STAT pathways by production of ROS.