PMID- 28800782 OWN - NLM STAT- MEDLINE DCOM- 20170901 LR - 20240326 IS - 1472-6882 (Electronic) IS - 1472-6882 (Linking) VI - 17 IP - 1 DP - 2017 Aug 12 TI - 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. PG - 401 LID - 10.1186/s12906-017-1909-7 [doi] LID - 401 AB - 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. FAU - Chiu, Jen-Hwey AU - Chiu JH AUID- ORCID: 0000-0003-3046-6250 AD - Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China. chiujh@mailsrv.ym.edu.tw. AD - Comprehensive Breast Health Center & Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China. chiujh@mailsrv.ym.edu.tw. AD - Division of General Surgery, Department of Surgery, Cheng-Hsin General Hospital, Taipei, Taiwan, Republic of China. chiujh@mailsrv.ym.edu.tw. FAU - Chen, Fang-Pey AU - Chen FP AD - Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China. AD - Center of Traditional Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China. FAU - Tsai, Yi-Fang AU - Tsai YF AD - Comprehensive Breast Health Center & Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China. AD - Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China. FAU - Lin, Man-Ting AU - Lin MT AD - Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China. FAU - Tseng, Ling-Ming AU - Tseng LM AD - Comprehensive Breast Health Center & Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China. lmtseng@vghtpe.gov.tw. AD - Department of Surgery, Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China. lmtseng@vghtpe.gov.tw. FAU - Shyr, Yi-Ming AU - Shyr YM AD - Comprehensive Breast Health Center & Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China. AD - Department of Surgery, Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China. LA - eng PT - Journal Article DEP - 20170812 PL - England TA - BMC Complement Altern Med JT - BMC complementary and alternative medicine JID - 101088661 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Drugs, Chinese Herbal) RN - 0 (Membrane Glycoproteins) RN - 7171WSG8A2 (BDNF protein, human) RN - EC 1.14.99.1 (Cyclooxygenase 2) RN - EC 2.7.10.1 (Protein-Tyrosine Kinases) RN - EC 2.7.10.1 (Receptor, trkB) RN - EC 2.7.10.1 (tropomyosin-related kinase-B, human) RN - EC 3.4.24.24 (Matrix Metalloproteinase 2) RN - EC 3.4.24.35 (Matrix Metalloproteinase 9) RN - EC 3.6.5.2 (cdc42 GTP-Binding Protein) RN - EC 3.6.5.2 (rac GTP-Binding Proteins) SB - IM MH - Brain-Derived Neurotrophic Factor/*metabolism MH - *Breast Neoplasms/metabolism/pathology MH - Cell Line, Tumor MH - Cell Movement/drug effects MH - Cyclooxygenase 2/metabolism MH - Drugs, Chinese Herbal/*adverse effects MH - Endothelial Cells/*drug effects/metabolism/pathology MH - Female MH - Human Umbilical Vein Endothelial Cells MH - Humans MH - Magnoliopsida/adverse effects MH - Matrix Metalloproteinase 2/metabolism MH - Matrix Metalloproteinase 9/metabolism MH - Membrane Glycoproteins/metabolism MH - Neoplasm Recurrence, Local/*etiology MH - Phytotherapy/*adverse effects MH - Plants, Medicinal/*adverse effects MH - Protein-Tyrosine Kinases/metabolism MH - Receptor, trkB MH - Signal Transduction MH - Up-Regulation MH - cdc42 GTP-Binding Protein/metabolism MH - rac GTP-Binding Proteins/metabolism PMC - PMC5554408 OTO - NOTNLM OT - BDNF OT - Breast cancer OT - Chinese herbal medicine OT - Endothelial cell COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: not applicable. CONSENT FOR PUBLICATION: not applicable. COMPETING INTERESTS: The authors declare that they have no competing interests. PUBLISHER'S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. EDAT- 2017/08/13 06:00 MHDA- 2017/09/02 06:00 PMCR- 2017/08/12 CRDT- 2017/08/13 06:00 PHST- 2016/11/11 00:00 [received] PHST- 2017/08/03 00:00 [accepted] PHST- 2017/08/13 06:00 [entrez] PHST- 2017/08/13 06:00 [pubmed] PHST- 2017/09/02 06:00 [medline] PHST- 2017/08/12 00:00 [pmc-release] AID - 10.1186/s12906-017-1909-7 [pii] AID - 1909 [pii] AID - 10.1186/s12906-017-1909-7 [doi] PST - epublish SO - BMC Complement Altern Med. 2017 Aug 12;17(1):401. doi: 10.1186/s12906-017-1909-7.