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

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.

• Authors: Li Tao, Fangtian Fan, Yuping Liu, Weidong Li, Lei Zhang, Junshan Ruan, Cunsi Shen, Xiaobo Sheng, Zhijie Zhu, Aiyun Wang, Wenxing Chen, Shile Huang, Yin Lu
• Journal: PloS one (PLoS One) Vol. 8 Issue 11 Pg. e81945 ( 2013) ISSN: 1932-6203 [Electronic] United States
• PMID: 24312384 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Furans
• STAT3 Transcription Factor
• STAT3 protein, human
• beta Catenin
• xanthatin
• GSK3B protein, human
• Glycogen Synthase Kinase 3 beta
• Glycogen Synthase Kinase 3

Topics

• Antineoplastic Agents (pharmacology, therapeutic use)
• Apoptosis
• Carcinoma, Non-Small-Cell Lung (enzymology, metabolism, pathology)
• Cell Line, Tumor
• Cell Proliferation
• Furans (pharmacology, therapeutic use)
• Glycogen Synthase Kinase 3 (antagonists & inhibitors, metabolism)
• Glycogen Synthase Kinase 3 beta
• Humans
• Lung Neoplasms (enzymology, metabolism, pathology)
• RNA Processing, Post-Transcriptional
• STAT3 Transcription Factor (antagonists & inhibitors, metabolism)
• beta Catenin (metabolism)