title: Tanshinone IIA inhibits breast cancer stem cells growth in vitro and in vivo through attenuation of IL-6/STAT3/NF-kB signaling pathways.
abstract: Cancer stem cells (CSCs) are maintained by inflammatory cytokines and signaling pathways. Tanshinone IIA (Tan-IIA) possesses anti-cancer and anti-inflammatory activities. The purpose of this study is to confirm the growth inhibition effect of Tan-IIA on human breast CSCs growth in vitro and in vivo and to explore the possible mechanism of its activity. Human breast CSCs were enriched and expanded under serum-free mammosphere culture condition, and identified through mammosphere formation, toluidine blue staining, immunofluorescence staining, and flow cytometry analysis of stemness markers of CD44/CD24 and ALDH, and tumorigenecity in vivo; the growth inhibition effect of Tan-IIA on human breast CSCs in vitro were tested by cell proliferation and mammosphere formation assays; inflammatory signaling pathway related protein expression in response to Tan-IIA, IL-6, STAT3, phospho-STAT3 (Tyr705), NF-κBp65 in cytoplasm and nucleus and cyclin D1 were evaluated with Western blotting; the growth inhibition effect of Tan-IIA on human breast CSCs growth were tested in vivo. A useful model of human breast CSCs for researching and developing the agents targeting CSCs was established. After Tan-IIA treatment, cell proliferation and mammosphere formation of CSCs were decreased significantly; the expression levels of IL-6, STAT3, phospho-STAT3 (Tyr705), NF-κBp65 in nucleus and cyclin D1 proteins were decreased significantly; the tumor growth and mean tumor weight were reduced significantly. Tan-IIA has the potential to target and kill CSCs, and can inhibit human breast CSCs growth both in vitro and in vivo through attenuation of IL-6/STAT3/NF-kB signaling pathways.
authors.affiliation: Laboratory of Geriatrics, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041, China.
authors.forename: Caiyu
authors.initials: C
authors.lastname: Lin
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.forename: Liuqi
authors.initials: L
authors.lastname: Yang
authors.forename: Huijie
authors.initials: H
authors.lastname: Guo
authors.forename: Xiujie
authors.initials: X
authors.lastname: Wang
mesh_terms: D045784:Abietanes / Q000494:pharmacology*; D000080924:Aldehyde Dehydrogenase 1 Family; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology*; D050697:Retinal Dehydrogenase / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics
chemical_list: D045784:Abietanes; D015850:Interleukin-6; D007527:Isoenzymes; D016328:NF-kappa B; D050796:STAT3 Transcription Factor; C021751:tanshinone; D000080924:Aldehyde Dehydrogenase 1 Family; C510223:ALDH1A1 protein, human; D050697:Retinal Dehydrogenase
keywords: BREAST CANCER; CANCER STEM CELLS; GROWTH INHIBITION; IL-6/STAT3/NF-kB SIGNALING PATHWAYS; TANSHINONE IIA