title: Salinomycin exerts anticancer effects on human breast carcinoma MCF-7 cancer stem cells via modulation of Hedgehog signaling.
abstract: Breast cancer tissue contains a small population of cells that have the ability to self-renew, these cells are known as breast cancer stem cells (BCSCs). The Hedgehog signal transduction pathway plays a central role in stem cell development, its aberrant activation has been shown to contribute to the development of breast cancer, making this pathway an attractive therapeutic target. Salinomycin (Sal) is a novel identified cancer stem cells (CSCs) killer, however, the molecular basis for its anticancer effects is not yet clear. In the current study, Sal's ability to modulate the activity of key elements in the Hedgehog pathway was examined in the human breast cancer cell line MCF-7, as well as in a subpopulation of cancer stem cells identified within this cancer cell line. We show here that Sal inhibits proliferation, invasion, and migration while also inducing apoptosis in MCF-7 cells. Interestingly, in a subpopulation of MCF-7 cells with the CD44(+)/CD24(-) markers and high ALDH1 levels indicative of BCSCs, modulators of Hedgehog signaling Smo and Gli1 were significantly down-regulated upon treatment with Sal. These results demonstrate that Sal also inhibits proliferation and induces apoptosis of BCSCs, further establishing it as therapeutically relevant in the context of breast cancers and also indicating that modulation of Hedgehog signaling is one potential mechanism by which it exerts these anticancer effects.
authors.affiliation: Department of Pathology, Dalian Medical University, Dalian 116044, PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Pathology, Dalian Medical University, Dalian 116044, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Ma
authors.affiliation: Department of Pathology, Dalian Medical University, Dalian 116044, PR China; The Key Laboratory of Tumor Stem Cell Research of Liaoning Province, Dalian Medical University, Dalian 116044, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Mao
authors.affiliation: Department of Pathology, Dalian Medical University, Dalian 116044, PR China.
authors.forename: Xiaotang
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Pathology, Dalian Medical University, Dalian 116044, PR China.
authors.forename: Zhenhuan
authors.initials: Z
authors.lastname: Hou
authors.affiliation: Department of Pathology, Dalian Medical University, Dalian 116044, PR China.
authors.forename: Shujun
authors.initials: S
authors.lastname: Fan
authors.affiliation: Department of Pathology, Dalian Medical University, Dalian 116044, PR China.
authors.forename: Bo
authors.initials: B
authors.lastname: Song
authors.affiliation: Department of Pathology, Dalian Medical University, Dalian 116044, PR China.
authors.forename: Huan
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Pathology, Dalian Medical University, Dalian 116044, PR China.
authors.forename: Jiazhi
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Pathology, Dalian Medical University, Dalian 116044, PR China.
authors.forename: Le
authors.initials: L
authors.lastname: Kang
authors.affiliation: Institute of Cancer Stem Cell, Dalian Medical University, Dalian 116044, PR China.
authors.forename: Pixu
authors.initials: P
authors.lastname: Liu
authors.affiliation: Institute of Cancer Stem Cell, Dalian Medical University, Dalian 116044, PR China.
authors.forename: Quentin
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Pathology, Dalian Medical University, Dalian 116044, PR China; The Key Laboratory of Tumor Stem Cell Research of Liaoning Province, Dalian Medical University, Dalian 116044, PR China. Electronic address: lilianhong9177@163.com.
authors.forename: Lianhong
authors.initials: L
authors.lastname: Li
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D061986:MCF-7 Cells; D015394:Molecular Structure; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D011714:Pyrans / Q000737:chemistry / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000378:metabolism; D014407:Tumor Cells, Cultured; D000071676:Zinc Finger Protein GLI1; D000095662:Polyether Polyketides
chemical_list: D000970:Antineoplastic Agents; D053823:Hedgehog Proteins; D011714:Pyrans; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1; C400551:GLI1 protein, human; C010327:salinomycin; D000095662:Polyether Polyketides
keywords: Breast carcinoma MCF-7; Cancer stem cells; Hedgehog signaling; Salinomycin