Aurora kinase A (AURKA) carries out an essential role in proliferation and involves in cisplatin resistance in various cancer cells. Overexpression of AURKA is associated with the poor prognosis of cancer patients. Thus, AURKA has been considered as a target for cancer therapy. Developing AURKA inhibitors became an important issue in cancer therapy. A natural compound emodin mainly extracted from rhubarbs possesses anti-cancer properties. However, the effect of emodin on AURKA has never been investigated. In the present study, molecular docking analysis indicated that emodin interacts with AURKA protein active site. We also found nine emodin analogues from Key Organic database by using ChemBioFinder software. Among that, one analogue 8L-902 showed a similar anti-cancer effect as emodin. The bindings of emodin and 8L-902 on AURKA protein were confirmed by cellular thermal shift assay. Furthermore, emodin inhibited the AURKA kinase activity in vitro and enhanced the cisplatin-DNA adduct level in a resistant ovarian cancer cell line. It seems that emodin may have the potential to inhibit cancer cell growth and enhance cisplatin therapy in cancer with resistance. Collectively, our finding reveals a novel AURKA inhibitor, emodin, which may be vulnerable to ovarian cancer therapy in the future.

中文翻译：

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天然蒽醌化合物大黄素作为一种新型极光 A 激酶抑制剂：一项初步研究

极光激酶 A (AURKA) 在增殖中发挥重要作用，并参与各种癌细胞的顺铂耐药性。AURKA 的过度表达与癌症患者的不良预后有关。因此，AURKA 被认为是癌症治疗的靶点。开发 AURKA 抑制剂成为癌症治疗中的一个重要问题。主要从大黄中提取的天然复合大黄素具有抗癌特性。然而，从未研究过大黄素对 AURKA 的影响。在本研究中，分子对接分析表明大黄素与 AURKA 蛋白活性位点相互作用。我们还使用 ChemBioFinder 软件从 Key Organic 数据库中发现了九种大黄素类似物。其中，一种类似物 8L-902 显示出与大黄素相似的抗癌作用。大黄素和 8L-902 与 AURKA 蛋白的结合通过细胞热位移测定得到证实。此外，大黄素在体外抑制 AURKA 激酶活性，并在耐药卵巢癌细胞系中提高顺铂-DNA 加合物水平。似乎大黄素可能具有抑制癌细胞生长和增强耐药癌症的顺铂治疗的潜力。总的来说，我们的发现揭示了一种新的 AURKA 抑制剂大黄素，它在未来可能容易受到卵巢癌治疗的影响。