Department of Pharmacology, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China.
PLoS One. 2013 Nov 28;8(11):e81945. doi: 10.1371/journal.pone.0081945. eCollection 2013.
Xanthatin, a sesquiterpene lactone purified from Xanthium strumarium L., possesses prominent anticancer activity. We found that disruption of GSK3β activity was essential for xanthatin to exert its anticancer properties in non-small cell lung cancer (NSCLC), concurrent with preferable suppression of constitutive activation of STAT3. Interestingly, inactivation of the two signals are two mutually exclusive events in xanthatin-induced cell death. Moreover, we surprisingly found that exposure of xanthatin failed to trigger the presumable side effect of canonical Wnt/β-Catenin followed by GSK3β inactivation. We further observed that the downregulation of STAT3 was required for xanthatin to fine-tune the risk. Thus, the discovery of xanthatin, which has ability to simultaneously orchestrate two independent signaling cascades, may have important implications for screening promising drugs in cancer therapies.
苍耳亭，一种从苍耳属植物中提取的倍半萜内酯，具有显著的抗癌活性。我们发现，GSK3β 活性的破坏对于苍耳亭发挥其在非小细胞肺癌（NSCLC）中的抗癌特性是必不可少的，同时更好地抑制了 STAT3 的组成性激活。有趣的是，在苍耳亭诱导的细胞死亡中，两条信号的失活是两个互斥的事件。此外，我们惊讶地发现，苍耳亭的暴露并没有引发可能的经典 Wnt/β-Catenin 随后的 GSK3β 失活的副作用。我们进一步观察到，STAT3 的下调对于苍耳亭微调风险是必需的。因此，苍耳亭的发现，它有能力同时协调两个独立的信号级联，对于筛选癌症治疗中有希望的药物可能具有重要意义。
