Xanthatin, a xanthanolide sesquiterpene lactone isolated from Xanthium strumarium L. (Asteraceae), has prominent anti-tumor activity. Initial mechanism of action studies suggested xanthatin triggered activation of Wnt/β-catenin. We examined the effects of xanthatin on signaling pathways in A459 lung cancer cells and mouse embryonic fibroblasts to ascertain requirements for xanthatin-induced cell death and tumor growth in xenografts. Genetic inactivation of GSK-3β, but not the related isoform GSK-3α, compromised xanthatin cytotoxicity while inactivation of β-catenin enhanced xanthatin-mediated cell death. These data provide insight into how xanthatin and related molecules could be effectively targeted toward certain tumors.

中文翻译：

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Xanthatin抗肿瘤细胞毒性通过糖原合酶激酶3β和β-catenin介导

Xanthatin是一种从黄药属（Asteraceae）分离的黄原醇倍半萜烯内酯，具有显着的抗肿瘤活性。最初的作用机制研究表明黄嘌呤触发了Wnt /β-catenin的激活。我们检查了黄嘌呤素对A459肺癌细胞和小鼠胚胎成纤维细胞信号通路的影响，以确定黄嘌呤素诱导的异种移植物中细胞死亡和肿瘤生长的要求。GSK-3β的遗传失活，而不是相关的同工型GSK-3α，损害了xanthatin的细胞毒性，而β-catenin的失活则增强了xanthatin介导的细胞死亡。这些数据提供了关于黄嘌呤和相关分子如何有效靶向某些肿瘤的见识。