Synephrine Hydrochloride Suppresses Esophageal Cancer Tumor Growth and Metastatic Potential through Inhibition of Galectin-3-AKT/ERK Signaling.

Published

Journal Article

A library consisting of 429 food-source compounds was used to screen the natural products with anticancer properties in esophageal squamous cell carcinoma (ESCC). We demonstrated for the first time that synephrine, an active compound isolated from leaves of citrus trees, markedly suppressed cell proliferation (inhibition rate with 20 μM synephrine at day 5:71.1 ± 5.8% and 75.7 ± 6.2% for KYSE30 and KYSE270, respectively) and colony formation (inhibition rate with 10 μM synephrine: 86.5 ± 5.9% and 82.3 ± 4.5% for KYSE30 and KYSE270, respectively), as well as migration (inhibition rate with 10 μM synephrine: 76.9 ± 4.4% and 62.2 ± 5.8% for KYSE30 and KYSE270, respectively) and invasion abilities (inhibition rate with 10 μM synephrine: 73.3 ± 7.5% and 75.3 ± 3.4% for KYSE30 and KYSE270, respectively) of ESCC cells in a dose-dependent manner, without significant toxic effect on normal esophageal epithelial cells. Mechanistically, quantitative proteomics and bioinformatics analyses were performed to explore the synephrine-regulated proteins. Western blot and qRT-PCR data indicated that synephrine may downregulate Galectin-3 to inactivate AKT and ERK pathways. In addition, we found that the sensitivity of ESCC to fluorouracil (5-FU) could be enhanced by synephrine. Furthermore, in vivo experiments showed that synephrine had significant antitumor effect on ESCC tumor xenografts in nude mice (inhibition rate with 20 mg/kg synephrine is 61.3 ± 20.5%) without observed side effects on the animals. Taken together, synephrine, a food-source natural product, may be a potential therapeutic strategy in ESCC.

Full Text

Duke Authors

Cited Authors

  • Xu, WW; Zheng, C-C; Huang, Y-N; Chen, W-Y; Yang, Q-S; Ren, J-Y; Wang, Y-M; He, Q-Y; Liao, H-X; Li, B

Published Date

  • September 5, 2018

Published In

Volume / Issue

  • 66 / 35

Start / End Page

  • 9248 - 9258

PubMed ID

  • 30113849

Pubmed Central ID

  • 30113849

Electronic International Standard Serial Number (EISSN)

  • 1520-5118

Digital Object Identifier (DOI)

  • 10.1021/acs.jafc.8b04020

Language

  • eng

Conference Location

  • United States