Novel Xanthone Derivatives Impair Growth and Invasiveness of Colon Cancer Cells In Vitro

Jakub Rech,Daniel Sypniewski,Henryk Marona,Ilona Bednarek,Wojciech Rogóż,Anna Waszkielewicz,Dorota Żelaszczyk,Natalia Szkaradek

doi:10.3390/biom11101480

Jakub Rech, Daniel Sypniewski + Show 6 more

Open Access

https://doi.org/10.3390/biom11101480

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Abstract

Natural xanthones are a large group of compounds from which promising anticancer properties could be further developed by chemical modifications. This study aimed to investigate the influence of four novel xanthone derivatives based on a naturally occurring xanthone skeleton on the invasiveness of colon cancer cells in vitro. First, the concentrations required to inhibit growth of three colorectal cancer cell lines to 50% (GI50) of all the studied compounds, as well as the natural xanthones used as a reference (gambogic acid and α-mangostin), have been established (MTS reduction test). Next, the assays determining several aspects of the GI25 xanthones influence on colorectal cancer cells, including cytotoxicity, migration and invasion potential, interaction with extracellular matrix and endothelial cells, as well as expression of selected invasiveness related genes have been performed. Our results demonstrate that these novel xanthone derivatives impair colorectal cancer proliferation, motility, adhesion to extracellular matrix and to endothelial cells, and also induce apoptosis and cell death. Moreover, their activity is comparable to cisplatin and 5-fluorouracil, used as reference compounds. Conducted research indicates our compounds for further research and development as novel drugs in colorectal cancer treatment.

Highlights

Colorectal cancer is the fourth most common tumor and a leading cause of cancer deaths worldwide
Levels of VEGF and intercellular adhesion molecule 1 (ICAM-1) released to cell culture supernatants were determined by ELISA
ELISA confirmed that ICAM-1 expression significantly decreased in all xanthone-treated cell cultures in comparison to untreated controls, and the strongest inhibitory influence was displayed by Comp

Summary

Introduction

Colorectal cancer is the fourth most common tumor and a leading cause of cancer deaths worldwide. There is an increasing tendency in the number of colorectal cancer patients, especially in societies with high or very high human development index, accounting for two-thirds of all colorectal cancer cases and 60% of deaths [1]. This is due to many unfavorable factors affecting the global population, including increasing age, genetic predispositions, as well as dietary and lifestyle factors, as the most significant [3,4]. Tumor invasion is determined by such pivotal processes as cancer metastasis and angiogenesis. These processes are complex, multistage, and involve many subtle alterations in cellular phenotype, such as motility, adhesion and invasion through the extracellular matrix (ECM), interaction with endothelial cells, or epithelial–

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