title: Elimination of ALDH+ breast tumor initiating cells by docosahexanoic acid and/or gamma tocotrienol through SHP-1 inhibition of Stat3 signaling.
abstract: Study investigated the ability of docosahexaenoic acid (DHA) alone and in combination with gamma-tocotrienol (γT3) to eliminate aldehyde dehydrogenase positive (ALDH+) cells and to inhibit mammosphere formation, biomarker and functional assay for tumor initiating cells (TICs), respectively, in human triple negative breast cancer cells (TNBCs), and investigated possible mechanisms of action. DHA upregulated Src homology region 2 domain-containing protein tyrosine phosphatase-1 (SHP-1) protein levels and suppressed levels of phosphorylated signal transducer and activator of transcription-3 (pStat3) and its downstream mediators c-Myc, and cyclin D1. siRNA to SHP-1 enhanced the percentage of ALDH+ cells and Stat-3 signaling, as well as inhibited, in part, the ability of DHA to reduce the percentage of ALDH+ cells and Stat-3 signaling. γT3 alone and in combination with DHA reduced ALDH+ TNBCs, up-regulated SHP-1 protein levels, and suppressed Stat-3 signaling. Taken together, data demonstrate the anti-TIC potential of achievable concentrations of DHA alone as well as in combination with γT3.
authors: Department of Nutritional Sciences, The University of Texas at Austin, Austin, Texas.
authors: Ailian
authors: A
authors: Xiong
authors: Department of Molecular Biosciences, The University of Texas at Austin, Austin, Texas.
authors: Weiping
authors: W
authors: Yu
authors: Department of Molecular Biosciences, The University of Texas at Austin, Austin, Texas.
authors: Yaobin
authors: Y
authors: Liu
authors: Department of Molecular Biosciences, The University of Texas at Austin, Austin, Texas.
authors: Bob G
authors: BG
authors: Sanders
authors: Department of Nutritional Sciences, The University of Texas at Austin, Austin, Texas.
authors: Kimberly
authors: K
authors: Kline
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000378:metabolism*; D000971:Antineoplastic Combined Chemotherapy Protocols; D045744:Cell Line, Tumor; D002839:Chromans / Q000494:pharmacology*; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000201:enzymology; D010766:Phosphorylation / Q000187:drug effects; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D064726:Triple Negative Breast Neoplasms / Q000201:enzymology* / Q000378:metabolism; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D002839:Chromans; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D014810:Vitamin E; D004281:Docosahexaenoic Acids; C013649:plastochromanol 8; D000444:Aldehyde Dehydrogenase; C509249:PTPN6 protein, human; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6
keywords: aldehyde dehydrogenase activity positive (ALDH+); cancer stem-like cells (CSCs); docosahexaenoic acid (DHA); gamma-tocotrienol (γT3); mammospheres; protein Src homology region 2 domain-containing tyrosine phosphatase (SHP-1); signal transducer and activator of transcription 3 (Stat-3); triple negative breast cancer (TNBC) cells; tumor initiating cells (TICs)