title: Curcumin Suppresses Phthalate-Induced Metastasis and the Proportion of Cancer Stem Cell (CSC)-like Cells via the Inhibition of AhR/ERK/SK1 Signaling in Hepatocellular Carcinoma.
abstract: Recent evidence indicating that phthalates promote cancer development, including cell proliferation, migration, and invasion, has raised public health concerns. Here, we show that bis(2-ethylhexyl) phthalate promotes the migration, invasion, and epithelial-mesenchymal transition of hepatocellular carcinoma cells. In addition, bis(2-ethylhexyl) phthalate increased the proportion of cancer stem cell (CSC)-like cells and stemness maintenance in vitro as well as tumor growth and metastasis in vivo. The various activities of curcumin, including anticancer, anti-inflammation, antioxidation, and immunomodulation, have been investigated extensively. Curcumin suppressed phthalate-induced cell migration, invasion, and epithelial-mesenchymal transition, decreased the proportion of CSC-like cells in hepatocellular carcinoma cell lines in vitro, and inhibited tumor growth and metastasis in vivo. We also reveal that curcumin suppressed phthalate-induced migration, invasion, and CSC-like cell maintenance through inhibition of the aryl hydrocarbon receptor/ERK/SK1/S1P3 signaling pathway. Our results suggest that curcumin may be a potential antidote for phthalate-induced cancer progression.
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University , Kaohsiung City 807, Taiwan.
authors.forename: Cheng-Fang
authors.initials: CF
authors.lastname: Tsai
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University , Kaohsiung City 807, Taiwan.
authors.forename: Tsung-Hua
authors.initials: TH
authors.lastname: Hsieh
authors.affiliation: Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital , Kaohsiung City 807, Taiwan.
authors.forename: Jau-Nan
authors.initials: JN
authors.lastname: Lee
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University , Kaohsiung City 807, Taiwan.
authors.forename: Chia-Yi
authors.initials: CY
authors.lastname: Hsu
authors.affiliation: Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital , Kaohsiung City 807, Taiwan.
authors.forename: Yu-Chih
authors.initials: YC
authors.lastname: Wang
authors.affiliation: Division of Hepatobiliary Pancreatic Surgery, Department of Surgery, Kaohsiung Medical University Hospital , Kaohsiung 807, Taiwan.
authors.forename: Kung-Kai
authors.initials: KK
authors.lastname: Kuo
authors.affiliation: Department of Biochemistry and Molecular Biology, National Cheng Kung University , Tainan 701, Taiwan.
authors.forename: Hua-Lin
authors.initials: HL
authors.lastname: Wu
authors.affiliation: Department of Biotechnology, Kaohsiung Medical University , Kaohsiung 807, Taiwan.
authors.forename: Chien-Chih
authors.initials: CC
authors.lastname: Chiu
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University , Kaohsiung City 807, Taiwan.|Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital , Kaohsiung City 807, Taiwan.
authors.forename: Eing-Mei
authors.initials: EM
authors.lastname: Tsai
authors.affiliation: Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University , Kaohsiung 807, Taiwan.
authors.forename: Po-Lin
authors.initials: PL
authors.lastname: Kuo
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D008297:Male; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism; D010795:Phthalic Acids / Q000633:toxicity; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000235:genetics / Q000378:metabolism*
chemical_list: D010795:Phthalic Acids; D018336:Receptors, Aryl Hydrocarbon; D051640:Small-Conductance Calcium-Activated Potassium Channels; C032279:phthalic acid; D048049:Extracellular Signal-Regulated MAP Kinases; D003474:Curcumin
keywords: cancer stem cells; curcumin; hepatocellular carcinoma; metastasis; phthalate; side population