1. Academic Validation
  2. Effects of Chinese medicinal herbs on expression of brain-derived Neurotrophic factor (BDNF) and its interaction with human breast cancer MDA-MB-231 cells and endothelial HUVECs

Effects of Chinese medicinal herbs on expression of brain-derived Neurotrophic factor (BDNF) and its interaction with human breast cancer MDA-MB-231 cells and endothelial HUVECs

  • BMC Complement Altern Med. 2017 Aug 12;17(1):401. doi: 10.1186/s12906-017-1909-7.
Jen-Hwey Chiu 1 2 3 Fang-Pey Chen 4 5 Yi-Fang Tsai 6 7 Man-Ting Lin 4 Ling-Ming Tseng 8 9 Yi-Ming Shyr 6 10
Affiliations

Affiliations

  • 1 Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China. [email protected].
  • 2 Comprehensive Breast Health Center & Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China. [email protected].
  • 3 Division of General Surgery, Department of Surgery, Cheng-Hsin General Hospital, Taipei, Taiwan, Republic of China. [email protected].
  • 4 Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China.
  • 5 Center of Traditional Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China.
  • 6 Comprehensive Breast Health Center & Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China.
  • 7 Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China.
  • 8 Comprehensive Breast Health Center & Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China. [email protected].
  • 9 Department of Surgery, Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China. [email protected].
  • 10 Department of Surgery, Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China.
Abstract

Background: Our previous study demonstrated that an up-regulation of the Brain-Derived Neurotrophic Factor (BDNF) signaling pathway is involved the mechanism causing the recurrence of triple negative breast Cancer. The aim of this study is to investigate the effects of commonly used Chinese medicinal herbs on MDA-MB-231 and HUVEC cells and how they interact with BDNF.

Methods: Human TNBC MDA-MB-231 cells and human endothelial HUVEC cells were used to explore the effect of commonly used Chinese herbal medicines on Cancer cells alone, on endothelial cells alone and on Cancer cell/endothelial cell interactions; this was done via functional studies, including migration and invasion assays. Furthermore, Western blot analysis and Real-Time PCR investigations were also used to investigate migration signal transduction, invasion signal transduction, and angiogenic signal transduction in these systems. Finally, the effect of the Chinese medicinal herbs on Cancer cell/endothelial cell interactions was assessed using co-culture and ELISA.

Results: In terms of autoregulation, BDNF up-regulated TrkB gene expression in both MDA-MB-231 and HUVEC cells. Furthermore, BDNF enhanced migration by MDA-MB-231 cells via Rac, Cdc42 and MMP, while also increasing the migration of HUVEC cells via MMP and COX-2 expression. As measured by ELISA, the Chinese herbal medicinal herbs A. membranaceus, P. lactiflora, L. chuanxiong, P. suffruticosa and L. lucidum increased BDNF secretion by MDA-MB-231 cells. Similarly, using a co-culture system with MDA-MB-231 cells, A. membranaceus and L. lucidum modulated BDNF-TrkB signaling by HUVEC cells.

Conclusion: We conclude that BDNF plays an important role in the metastatic interaction between MDA-MB-231 and HUVEC cells. Some Chinese medicinal herbs are able to enhance the BDNF-related metastatic potential of the interaction between Cancer cells and endothelial cells. These findings provide important information that should help with the development of integrated medical therapies for breast Cancer patients.

Keywords

BDNF; Breast cancer; Chinese herbal medicine; Endothelial cell.

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