A vanillin derivative suppresses the growth of HT29 cells through the Wnt/β-catenin signaling pathway

Wantong Ma; Xue Li; Peng Song; Qianqian Zhang; Zhengrong Wu; Jianhui Wang; Xiaofeng Li; Ruixiang Xu; Wenbin Zhao; Yuheng Liu; Huanxiang Liu; Xiaojun Yao; Xiaoliang Tang; Peng Chen

doi:10.1016/j.ejphar.2019.01.047

A vanillin derivative suppresses the growth of HT29 cells through the Wnt/β-catenin signaling pathway

Eur J Pharmacol. 2019 Apr 15:849:43-49. doi: 10.1016/j.ejphar.2019.01.047. Epub 2019 Jan 29.

Authors

Wantong Ma¹, Xue Li², Peng Song¹, Qianqian Zhang¹, Zhengrong Wu¹, Jianhui Wang³, Xiaofeng Li³, Ruixiang Xu¹, Wenbin Zhao¹, Yuheng Liu¹, Huanxiang Liu¹, Xiaojun Yao⁴, Xiaoliang Tang⁵, Peng Chen⁶

Affiliations

¹ School of Pharmacy, Lanzhou University, 199 Donggang West Road, Lanzhou 730000, PR China.
² College of Chemistry and Chemical Engineering, Lanzhou University, 222 Tianshui South Road, Lanzhou 730000, PR China.
³ Department of Pathology, School of Medicine, Yale University, 310 Cedar Street, New Haven 06510, USA.
⁴ Macau Institute for Applied Research in Medicine and Health, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau, PR China. Electronic address: xjyao@must.edu.mo.
⁵ College of Chemistry and Chemical Engineering, Lanzhou University, 222 Tianshui South Road, Lanzhou 730000, PR China. Electronic address: tangxiaol@lzu.edu.cn.
⁶ School of Pharmacy, Lanzhou University, 199 Donggang West Road, Lanzhou 730000, PR China. Electronic address: chenpeng@lzu.edu.cn.

PMID: 30707959
DOI: 10.1016/j.ejphar.2019.01.047

Abstract

Colorectal cancer (CRC) is a common malignancy and the leading cause of cancer death worldwide. According to previous studies, vanillin possesses pharmacological and anticancer activities. In this work, we have modified the structure of vanillin to obtain a vanillin derivative called 4-(1H-imidazo [4,5-f][1,10]-phenanthrolin-2-yl)-2-methoxyphenol (IPM711), which has improved anticancer activity. The present study is intended to explore the anti-colorectal cancer activity of IPM711 in HT29 and HCT116 cells. The results of this study suggest that IPM711 can inhibit the growth, invasion and migration of HT29 and HCT116 cells. Western blot and molecular docking showed that IPM711 could bind to a Wnt/β-catenin signaling receptor to inhibit cell growth, invasion and migration in HT29 cells. Based on these results, IPM711 is a promising anticancer drug candidate for human colorectal cancer therapy.

Keywords: Colorectal cancer; Invasion; Migration; Vanillin derivative; Wnt/β-catenin.

MeSH terms

Antineoplastic Agents / chemistry*
Antineoplastic Agents / metabolism
Antineoplastic Agents / pharmacology*
Benzaldehydes / chemistry*
Benzaldehydes / metabolism
Benzaldehydes / pharmacology*
Cell Movement / drug effects
Cell Proliferation / drug effects
Frizzled Receptors / chemistry
Frizzled Receptors / metabolism
HCT116 Cells
HT29 Cells
Humans
Molecular Docking Simulation
Protein Conformation
Wnt Signaling Pathway / drug effects*

Substances

Antineoplastic Agents
Benzaldehydes
FZD1 protein, human
Frizzled Receptors
vanillin