Aloe-emodin inhibits HER-2 expression through the downregulation of Y-box binding protein-1 in HER-2-overexpressing human breast cancer cells
Metrics: PDF 1238 views | HTML 2291 views | ?
Jui-Wen Ma1, Chao-Ming Hung2,3, Ying-Chao Lin4,5,6, Chi-Tang Ho7, Jung-Yie Kao1, Tzong-Der Way8,9
1Institute of Biochemistry, College of Life Science, National Chung Hsing University, Taichung, Taiwan
2Department of General Surgery, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan
3School of Medicine, I-Shou University, Kaohsiung, Taiwan
4Division of Neurosurgery, Buddhist Tzu Chi General Hospital, Taichung Branch, Taiwan
5School of Medicine, Tzu Chi University, Hualien, Taiwan
6Department of Medical Imaging and Radiological Science, Central Taiwan University of Science and Technology, Taichung, Taiwan
7Department of Food Science, Rutgers University, New Brunswick, New Jersey, USA
8Department of Biological Science and Technology, College of Biopharmaceutical and Food Sciences, China Medical University, Taichung, Taiwan
9Department of Health and Nutrition Biotechnology, College of Health Science, Asia University, Taichung, Taiwan
Tzong-Der Way, email: firstname.lastname@example.org
Jung-Yie Kao, email: email@example.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
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.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.