Cytotoxic activities of Telectadium dongnaiense and its constituents by inhibition of the Wnt/β-catenin signaling pathway.

Abstract

BACKGROUND:

Wnt/β-catenin signaling pathway is a potential target for the treatment of human colon cancer. Thus, the inhibitory effects of various plant extracts on cell proliferation and Wnt signal transduction were evaluated to discover a Wnt signaling inhibitor.

PURPOSE:

The present study aimed to investigate the cytotoxicity involved in Wnt pathway of the MeOH extract from Telectadium dongnaiense bark (TDB) and to identify its bioactive constituents by bioassay-guided fractionation.

METHODS:

The sulforhodamine B-based proliferation assay and the β-catenin/TCF-responsive reporter gene assay were employed as screening systems. The isolation and identification of compounds were elucidated on the basis of spectroscopic methods. Inhibitory effects on the expression levels of Wnt target genes were determined by real-time PCR and western blotting.

RESULTS:

The extract of TDB most strongly inhibited cell proliferation and TOPflash activity (IC50 = 1.5 and 2.0 µg/ml), which was correlated with its inhibitory effects on the expression of Wnt target genes. Three major compounds were isolated from bioactive fractions and were identified as 1,4-dicaffeoylquinic acid (1), quercetin 3-rutinoside (2), and periplocin (3). Only compound 3 showed anti-proliferative activity (IC50 = 0.06 µM) and exhibited Wnt signaling inhibitory effects in HCT116 colon cancer cells.

CONCLUSIONS:

This study contributes to understanding the cytotoxic properties of TDB extract and its constituents and provides a potent strategy for its further application.

• Authors: Won Kyung Kim, Duc-Hiep Bach, Hyung Won Ryu, Jedo Oh, Hyen Joo Park, Ji-Young Hong, Hyuk-Hwan Song, Sangmi Eum, Tran The Bach, Sang Kook Lee
• Journal: Phytomedicine : international journal of phytotherapy and phytopharmacology (Phytomedicine) Vol. 34 Pg. 136-142 (Oct 15 2017) ISSN: 1618-095X [Electronic] Germany
• PMID: 28899495 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 The Authors. Published by Elsevier GmbH.. All rights reserved.

Chemical References

• Antineoplastic Agents, Phytogenic
• Plant Extracts

Topics

• Antineoplastic Agents, Phytogenic (pharmacology)
• Apocynaceae (chemistry)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Colonic Neoplasms (pathology)
• HCT116 Cells
• Humans
• Plant Bark (chemistry)
• Plant Extracts (pharmacology)
• Signal Transduction (drug effects)
• Wnt Signaling Pathway (drug effects)