Aloe-emodin inhibits HER-2 expression through the downregulation of Y-box binding protein-1 in HER-2-overexpressing human breast cancer cells

// Jui-Wen Ma 1 , Chao-Ming Hung 2, 3 , Ying-Chao Lin 4, 5, 6 , Chi-Tang Ho 7 , Jung-Yie Kao 1 , Tzong-Der Way 8, 9 1 Institute of Biochemistry, College of Life Science, National Chung Hsing University, Taichung, Taiwan 2 Department of General Surgery, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan 3 School of Medicine, I-Shou University, Kaohsiung, Taiwan 4 Division of Neurosurgery, Buddhist Tzu Chi General Hospital, Taichung Branch, Taiwan 5 School of Medicine, Tzu Chi University, Hualien, Taiwan 6 Department of Medical Imaging and Radiological Science, Central Taiwan University of Science and Technology, Taichung, Taiwan 7 Department of Food Science, Rutgers University, New Brunswick, New Jersey, USA 8 Department of Biological Science and Technology, College of Biopharmaceutical and Food Sciences, China Medical University, Taichung, Taiwan 9 Department of Health and Nutrition Biotechnology, College of Health Science, Asia University, Taichung, Taiwan Correspondence to: Tzong-Der Way, email: tdway@mail.cmu.edu.tw Jung-Yie Kao, email: biosjyk@gmail.com Keywords: HER-2-overexpressing breast cancer cells, aloe-emodin, Y-box binding protein-1, ILK/Akt/mTOR signaling pathway, epithelial-mesenchymal transition Received: January 06, 2016      Accepted: June 12, 2016      Published: July 06, 2016 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.