title: 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: Department of Pharmacology, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China.
authors: Li
authors: L
authors: Tao
authors: Fangtian
authors: F
authors: Fan
authors: Yuping
authors: Y
authors: Liu
authors: Weidong
authors: W
authors: Li
authors: Lei
authors: L
authors: Zhang
authors: Junshan
authors: J
authors: Ruan
authors: Cunsi
authors: C
authors: Shen
authors: Xiaobo
authors: X
authors: Sheng
authors: Zhijie
authors: Z
authors: Zhu
authors: Aiyun
authors: A
authors: Wang
authors: Wenxing
authors: W
authors: Chen
authors: Shile
authors: S
authors: Huang
authors: Yin
authors: Y
authors: Lu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005663:Furans / Q000494:pharmacology / Q000627:therapeutic use*; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D012323:RNA Processing, Post-Transcriptional; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D005663:Furans; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D051176:beta Catenin; C022186:xanthatin; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3