title: Curcumin inhibits metastasis in human papillary thyroid carcinoma BCPAP cells via down-regulation of the TGF-β/Smad2/3 signaling pathway.
abstract: Thyroid cancers usually possess a good prognosis while the risks of recurrence and metastasis turn out to be a disturbing issue. Curcumin [bis(4-hydroxy-3-methoxy-phenyl)-1,6-heptadiene-3,5-dione] is a natural polyphenolic compound mainly found in turmeric (Curcuma longa). Our previous studies have demonstrated that curcumin showed proliferation-inhibitory and apoptosis-inducing effects on K1 papillary thyroid cancer cells. However, the mechanism underlying the inhibition effects of curcumin on thyroid cancer cells remains unclear. Herein, we demonstrated that curcumin remarkably increased the expression of the epithelial marker E-cadherin and repressed the expression of the mesenchymal marker vimentin in human papillary thyroid carcinoma BCPAP cells. Curcumin also suppressed multiple metastatic steps of BCPAP cells, including cell attachment, spreading as well as migration. In addition, the transcription, secretion and activation of matrix metalloproteinases (MMPs) induced by transforming growth factor-β1 (TGF-β1) in BCPAP cells were mitigated upon curcumin treatment. Further evidence showed that curcumin decreased TGF-β1-mediated phosphorylation of Smad2 and Smad3. These results revealed that curcumin inhibited the TGF-β1-induced epithelial-mesenchymal transition (EMT) via down-regulation of Smad2/3 signaling pathways. Our findings provide new evidence that the anti-metastatic and anti-EMT activities of curcumin may contribute to the development of chemo-preventive agents for thyroid cancer treatment.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, China; Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu, China.
authors.forename: Xian
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China.
authors.forename: Chiyu
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu, China.
authors.forename: Jiandong
authors.initials: J
authors.lastname: Bao
authors.affiliation: Department of Endocrinology & Metabolism and Institute of Endocrinology, The First Hospital of China Medical University, Shenyang, Liaoning, China.
authors.forename: Haixia
authors.initials: H
authors.lastname: Guan
authors.affiliation: Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu, China.
authors.forename: Huixin
authors.initials: H
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China. Electronic address: lurr@jiangnan.edu.cn.
authors.forename: Rongrong
authors.initials: R
authors.lastname: Lu
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, China. Electronic address: molpharm@163.com.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, China. Electronic address: yangsun@nju.edu.cn.
authors.forename: Yang
authors.initials: Y
authors.lastname: Sun
mesh_terms: D002277:Carcinoma / Q000188:drug therapy / Q000473:pathology*; D002291:Carcinoma, Papillary; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D003474:Curcumin / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D006801:Humans; D015398:Signal Transduction / Q000187:drug effects*; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000188:drug therapy / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053782:Transforming Growth Factor beta3 / Q000378:metabolism*
chemical_list: D016212:Transforming Growth Factor beta; D053782:Transforming Growth Factor beta3; D003474:Curcumin
keywords: Curcumin; Human papillary thyroid carcinoma; Matrix metalloproteinases; Metastasis; TGF-β/Smad2/3