Format

Send to

Choose Destination
J Cell Biochem. 2018 Feb;119(2):2231-2239. doi: 10.1002/jcb.26385. Epub 2017 Oct 27.

FGFR2 regulation by picrasidine Q inhibits the cell growth and induces apoptosis in esophageal squamous cell carcinoma.

Author information

1
China-US (Henan) Hormel Cancer Institute, Zhengzhou, Henan, P.R. China.
2
Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, P.R. China.
3
The Hormel Institute, University of Minnesota, Austin, Minnesota.

Abstract

Fibroblast growth factor receptor (FGFR) 2 and its downstream signaling cascades, PI3 K/AKT/mTOR is playing an important role in cell survival and proliferations. In this study, we firstly found that picrasidine Q (PQ), an alkaloid component extracted from Angelica keiskei species, has the capacity of anti-cell transformation and anti-cancer. After ligand shape similarity approach of PQ, we found that PQ targeted FGFR 2 and verified by FGFR2 kinase assay as well as computational docking model. FGFR2 highly expressed in esophageal cancer tissues and PQ inhibited fibroblast growth factor (FGF)-induced cell transformation. Furthermore, PQ inhibited cell proliferation and induced cell cycle arrest and apoptosis in KYSE30, KYSE410, and KYSE450 esophageal squamous cell carcinoma (ESCC) cells. It was confirmed by detecting of biological markers such as cyclinD1, cyclinD3 and cyclinB1 for cell cycle or cleaved caspase-7, caspase-3, and PARP for apoptosis. PQ targeting of FGFR2 kinase activities suppressed downstream target proteins including phosphorylation of AKT and mTOR but not MEK/ERK signaling pathways. Taken together, our results are the first to identify that PQ might be a chemopreventive and chemotherapeutic agent by direct targeting FGFR2 and inhibiting cell proliferation of ESCC cells.

KEYWORDS:

AKT/mTOR signaling pathways; FGFR2; esophageal squamous cell carcinoma; picrasidine Q (PQ)

PMID:
28857247
PMCID:
PMC5954433
DOI:
10.1002/jcb.26385
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center