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PLoS One. 2013 Nov 28;8(11):e81945. doi: 10.1371/journal.pone.0081945. eCollection 2013.

Concerted suppression of STAT3 and GSK3β is involved in growth inhibition of non-small cell lung cancer by Xanthatin.

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  • 1Department of Pharmacology, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China.

Abstract

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.

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