Euxanthone exhibits anti-proliferative and anti-invasive activities in hepatocellular carcinoma by inducing pyroptosis: preliminary results
Euxanthone exhibits anti-proliferative and anti-invasive activities in hepatocellular carcinoma by inducing pyroptosis: preliminary results
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DOI：
10.26355/eurrev_201812_16511
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发表时间：
2018-12-01
影响因子：
3.3
通讯作者：
Wu, F-L
中科院分区：
文献类型：
--
作者：
Chen, Y-F;Qi, H-Y;Wu, F-L
目的：肝细胞癌（HCC）是癌症相关死亡的最常见原因之一。 Euxanthone 是从远志中提取的氧杂蒽酮化合物，具有多种药理活性。本工作旨在探讨euxanthone在HCC中是否具有抗癌活性。患者和方法：收集组织标本，分别通过qRT-PCR和Western blot检测标记蛋白的mRNA和蛋白表达。通过CCK-8测定评估活细胞数。 TUNEL 测定用于确定细胞死亡。通过伤口愈合来测量细胞迁移。通过transwell实验测量细胞侵袭。建立异种移植模型来评估euxanthone在体内的功效。结果：我们证明HCC组织和HCC细胞系呈现较低的caspase-1、IL-1β和IL-18表达。 Euxanthone 显着抑制 HCC 细胞的增殖并诱导细胞死亡。此外，euxanthone 抑制细胞迁移和侵袭。同时，我们的结果表明，euxanthone 以 caspase-2 依赖性方式促进细胞死亡。体内数据还表明，euxanthone 抑制肿瘤生长并促进焦亡细胞死亡。结论：我们表明，euxanthone 可能是抗癌药物的候选者，并为 HCC 患者提供临床益处。
OBJECTIVE: Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related deaths. Euxanthone, a xanthone compound extracted from Polygala caudata, possesses a variety of pharmacological activities. This work aimed to explore whether euxanthone exhibits anti-cancer activities in HCC.PATIENTS AND METHODS: Tissue specimen was collected and the mRNA and protein expression of marker proteins were detected by qRT-PCR and Western blot, respectively. The viable cell number was assessed by CCK-8 assay. TUNEL assay was utilized to determine cell death. Cell migration was measured by Wound healing. Cell invasion was measured by transwell assay. Xenograft model was established to evaluate the efficacy of euxanthone in vivo.RESULTS: We demonstrated that HCC tissue and HCC cell line presented with lower expression of caspase-1, IL-1 beta, and IL-18. Euxanthone markedly suppressed the proliferation of HCC cells and induced cell death. In addition, euxanthone inhibited cell migration and invasion. Meanwhile, our results showed that euxanthone promoted cell death in a caspase-2 dependent manner. In vivo data also showed that euxanthone suppressed tumor growth and promoted pyroptotic cell death.CONCLUSIONS: We showed that that euxanthone may be a candidate of anticancer agent and provide clinical benefits for patients with HCC.