title: Curcumin Suppresses Lung Cancer Stem Cells via Inhibiting Wnt/β-catenin and Sonic Hedgehog Pathways.
abstract: Cancer stem cells (CSCs) are highly implicated in the progression of human cancers. Thus, targeting CSCs may be a promising strategy for cancer therapy. Wnt/β-catenin and Sonic Hedgehog pathways play an important regulatory role in maintaining CSC characteristics. Natural compounds, such as curcumin, possess chemopreventive properties. However, the interventional effect of curcumin on lung CSCs has not been clarified. In the present study, tumorsphere formation assay was used to enrich lung CSCs from A549 and H1299 cells. We showed that the levels of lung CSC markers (CD133, CD44, ALDHA1, Nanog and Oct4) and the number of CD133-positive cells were significantly elevated in the sphere-forming cells. We further illustrated that curcumin efficiently abolished lung CSC traits, as evidenced by reduced tumorsphere formation, reduced number of CD133-positive cells, decreased expression levels of lung CSC markers, as well as proliferation inhibition and apoptosis induction. Moreover, we demonstrated that curcumin suppressed the activation of both Wnt/β-catenin and Sonic Hedgehog pathways. Taken together, our data suggested that curcumin exhibited its interventional effect on lung CSCs via inhibition of Wnt/β-catenin and Sonic Hedgehog pathways. These novel findings could provide new insights into the potential therapeutic application of curcumin in lung CSC elimination and cancer intervention. Copyright © 2017 John Wiley & Sons, Ltd.
authors.affiliation: Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
authors.forename: Jian-Yun
authors.initials: JY
authors.lastname: Zhu
authors.affiliation: Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
authors.forename: Shi-Jia
authors.initials: SJ
authors.lastname: Wang
authors.affiliation: Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
authors.forename: Xiao-Qian
authors.initials: XQ
authors.lastname: Wang
authors.affiliation: Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Meng
authors.affiliation: Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
authors.forename: Ming-Ming
authors.initials: MM
authors.lastname: Zhu
authors.affiliation: Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Ma
authors.affiliation: Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Huang
authors.affiliation: Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Wu
authors.affiliation: Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
authors.forename: Chun-Feng
authors.initials: CF
authors.lastname: Xie
authors.affiliation: Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
authors.forename: Xiao-Ting
authors.initials: XT
authors.lastname: Li
authors.affiliation: Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
authors.forename: Shan-Shan
authors.initials: SS
authors.lastname: Geng
authors.affiliation: Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
authors.forename: Jie-Shu
authors.initials: JS
authors.lastname: Wu
authors.affiliation: Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
authors.forename: Cai-Yun
authors.identifier: http://orcid.org/0000-0002-5402-3713
authors.initials: CY
authors.lastname: Zhong
authors.affiliation: Department of Clinical Nutrition, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China.
authors.forename: Hong-Yu
authors.initials: HY
authors.lastname: Han
mesh_terms: D017209:Apoptosis; D049109:Cell Proliferation / Q000187:drug effects; D003474:Curcumin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D053823:Hedgehog Proteins / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D015398:Signal Transduction; D060449:Wnt Signaling Pathway / Q000235:genetics*
chemical_list: D053823:Hedgehog Proteins; C509239:SHH protein, human; D003474:Curcumin
keywords: Sonic Hedgehog pathway; Wnt/β-catenin pathway; curcumin; inhibition; lung cancer stem cells