Comparison of anticarcinogenic properties of Viburnum opulus and its active compound p-coumaric acid on human colorectal carcinoma

Abstract

Resistance to therapeutic agents and the highly toxic side effects of synthetic drugs has spurred new research in the treatmentof colon cancer, which has high morbidity and mortality ratios. This study aims to clarify the molecular mechanisms of the anticarcinogenic properties of methanol extract of Viburnum opulus L. (EVO)and its main active compound, trans-p-coumaric acid (p-CA),on human colon cancer cells (DLD-1, HT-29, SW-620, Caco-2) and healthy colon epithelial cells (CCD-18Co). The effects of EVO oncontrolled cell death (apoptosis) and the cell division cycle were determined by flow cytometry. Alteration in mRNA and protein expressions of switch genes in colorectal carcinoma (APC, MLH1, TP53, SMAD4, KRAS, and BRAF) were determined by qRT-PCR andWestern blot, respectively. Our results show that EVO possesses a strong reducing capacity and free-radical scavenging activity. HPLCanalyses prove that p-CAis the main compound of EVO. EVO and p-CA inhibit the proliferation of human colon cancer cells DLD-1and HT-29 in a dose-dependent manner. EVO increases apoptosis of DLD-1 cells and halts the cell cycle in the G2 stage in HT-29 cells.mRNA and protein expressions of p53 and SMAD-4 are upregulated, while BRAFs are downregulated. The results were directly proportional to p-CA. EVO and p-CA up- and downregulate switch genes and protein expressions of DLD-1 cells, which alter the expressionof 186 other genes. This is the first study of pharmacological exploration of V.opulus in human colon cancer. Its antiproliferative effectsmay be due to the presence of p-CA.