Inhibitory Effect of CAPE and Kaempferol in Colon Cancer Cell Lines-Possible Implications in New Therapeutic Strategies.

Liviuta Budisan,Atanas Atanasov,Calin Ionescu,Roxana Cojocneanu,Oana Zanoaga,Cristian Moldovan,Laura Pop,Alexandru Barbat,Cornelia Braicu,Ioana Berindan-Neagoe,Lajos Raduly,Alexandru Irimie,Ancuta Jurj,Diana Gulei,Adrian Tigu,Alin Moldovan

doi:10.3390/ijms20051199

Abstract

Background: Phytochemicals are natural compounds synthesized as secondary metabolites in plants and represent an important source of molecules with therapeutic applications. Attention is accorded to their potential in anti-cancer therapies as single agents or adjuvant treatment. Herby, we evaluated the in vitro effects of a panel of natural compounds with focus on caffeic acid phenethyl ester (CAPE) and Kaempferol for the treatment of human colon cancer. Methods: We exposed two human colon cancer cell lines, RKO and HCT-116, followed by functional examination of cell viability, cell proliferation and invasion, cell cycle, apoptosis, and autophagy. Modifications in gene expression were investigated through microarray and detection of existing mutations and finding of new ones was done with the help of Next Generation Sequencing (NGS). Results: Both CAPE and Kaempferol inhibit cell proliferation, motility and invasion, and stimulate apoptosis and autophagy, concomitant with modifications in coding and noncoding genes’ expression. Moreover, there are pathogenic mutations that are no longer found upon treatment with CAPE and Kaempferol. Conclusions: Our findings indicate that CAPE and Kaempferol have the ability to negatively influence the development and advancement of colon cancer in vitro by specifically altering the cells at the molecular level; this activity can be exploited in possible adjuvant therapies once the optimal dose concentration with minimal side effects but with cancer inhibitory activity is set in vivo.

Highlights

According to Globocan 2018 data, colon cancer is ranking as the third most common site of cancer and the second one in terms of mortality [1]
Even if the impact of polyphenols was demonstrated in the beginning of traditional medicine, nowadays they are associated with modifications in coding and noncoding gene expression or epigenetic events [7,9]; these novel data are backed up by the latest progresses in the “omics” approaches [11]
In order to assess the compounds with potential therapeutic value in colon cancer we tested the efficiency of caffeic acid phenethyl ester (CAPE), Kaempferol, Morin, EGCG, Daidzein, and Genistein in different concentrations on RKO, HCT-116, HT-29, and DLD-1 colon cancer cell lines in terms of inhibition of cell viability in a dose-dependent manner

Summary

Introduction

According to Globocan 2018 data, colon cancer is ranking as the third most common site of cancer and the second one in terms of mortality [1]. Associated with antioxidant properties and ability to prevent the formation of free radicals, current studies reveal a more complex protective action at cellular and molecular levels, with important application in disease prevention or treatment. These evidences are supported by epidemiological data [9,10]. Conclusions: Our findings indicate that CAPE and Kaempferol have the ability to negatively influence the development and advancement of colon cancer in vitro by altering the cells at the molecular level; this activity can be exploited in possible adjuvant therapies once the optimal dose concentration with minimal side effects but with cancer inhibitory activity is set in vivo

Methods

Results

Discussion

Conclusion