title: Aloe-emodin inhibits HER-2 expression through the downregulation of Y-box binding protein-1 in HER-2-overexpressing human breast cancer cells.
abstract: Human epidermal growth factor receptor-2 (HER-2)-positive breast cancer tends to be aggressive, highly metastatic, and drug resistant and spreads rapidly. Studies have indicated that emodin inhibits HER-2 expression. This study compared the HER-2-inhibitory effects of two compounds extracted from rhubarb roots: aloe-emodin (AE) and rhein. Our results indicated that AE exerted the most potent inhibitory effect on HER-2 expression. Treatment of HER-2-overexpressing breast cancer cells with AE reduced tumor initiation, cell migration, and cell invasion. AE was able to suppress YB-1 expression, further suppressing downstream HER-2 expression. AE suppressed YB-1 expression through the inhibition of Twist in HER-2-overexpressing breast cancer cells. Our data also found that AE inhibited cancer metastasis and cancer stem cells through the inhibition of EMT. Interestingly, AE suppressed YB-1 expression through the downregulation of the intracellular integrin-linked kinase (ILK)/protein kinase B (Akt)/mTOR signaling pathway in HER-2-overexpressing breast cancer cells. In vivo study showed the positive result of antitumor activity of AE in nude mice injected with human HER-2-overexpressing breast cancer cells. These findings suggest the possible application of AE in the treatment of HER-2-positive breast cancer.
authors.affiliation: Institute of Biochemistry, College of Life Science, National Chung Hsing University, Taichung, Taiwan.
authors.forename: Jui-Wen
authors.initials: JW
authors.lastname: Ma
authors.affiliation: Department of General Surgery, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan.|School of Medicine, I-Shou University, Kaohsiung, Taiwan.
authors.forename: Chao-Ming
authors.initials: CM
authors.lastname: Hung
authors.affiliation: Division of Neurosurgery, Buddhist Tzu Chi General Hospital, Taichung Branch, Taiwan.|School of Medicine, Tzu Chi University, Hualien, Taiwan.|Department of Medical Imaging and Radiological Science, Central Taiwan University of Science and Technology, Taichung, Taiwan.
authors.forename: Ying-Chao
authors.initials: YC
authors.lastname: Lin
authors.affiliation: Department of Food Science, Rutgers University, New Brunswick, New Jersey, USA.
authors.forename: Chi-Tang
authors.initials: CT
authors.lastname: Ho
authors.affiliation: Institute of Biochemistry, College of Life Science, National Chung Hsing University, Taichung, Taiwan.
authors.forename: Jung-Yie
authors.initials: JY
authors.lastname: Kao
authors.affiliation: Department of Biological Science and Technology, College of Biopharmaceutical and Food Sciences, China Medical University, Taichung, Taiwan.|Department of Health and Nutrition Biotechnology, College of Health Science, Asia University, Taichung, Taiwan.
authors.forename: Tzong-Der
authors.initials: TD
authors.lastname: Way
mesh_terms: D000880:Anthraquinones / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000378:metabolism / Q000628:therapy*; D063646:Carcinogenesis / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D015536:Down-Regulation; D004642:Emodin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D005960:Glucosides / Q000627:therapeutic use*; D006801:Humans; D009362:Neoplasm Metastasis; D008517:Phytotherapy; D018517:Plant Roots; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D012250:Rheum / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D014407:Tumor Cells, Cultured; D051840:Y-Box-Binding Protein 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D000880:Anthraquinones; D004642:Emodin; D005960:Glucosides; D051057:Proto-Oncogene Proteins c-akt; D018719:Erb-b2 Receptor Tyrosine Kinases; D058570:TOR Serine-Threonine Kinases; D051840:Y-Box-Binding Protein 1; C070856:YBX1 protein, human; C407723:aloe-emodin 1-O-glucopyranoside; C508053:ERBB2 protein, human; C020491:rhein
keywords: HER-2-overexpressing breast cancer cells; ILK/Akt/mTOR signaling pathway; Y-box binding protein-1; aloe-emodin; epithelial-mesenchymal transition