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; Chao-Ming Hung; Ying-Chao Lin; Chi-Tang Ho; Jung-Yie Kao; Tzong-Der Way

doi:10.18632/oncotarget.10410

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This article has been corrected. Correction in: Oncotarget. 2019; 10:5727-5729.

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, Chao-Ming Hung, Ying-Chao Lin, Chi-Tang Ho, Jung-Yie Kao and Tzong-Der Way _

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Oncotarget. 2016; 7:58915-58930. https://doi.org/10.18632/oncotarget.10410

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Abstract

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

Correspondence to:

Tzong-Der Way, email: [email protected]

Jung-Yie Kao, email: [email protected]

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.

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

Abstract