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 treatment of 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 on controlled 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 and Western blot, respectively. Our results show that EVO possesses a strong reducing capacity and free-radical scavenging activity. HPLC analyses prove that p -CAis the main compound of EVO. EVO and p -CA inhibit the proliferation of human colon cancer cells DLD-1 and 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 expression of 186 other genes. This is the first study of pharmacological exploration of V.opulus in human colon cancer. Its antiproliferative effects may be due to the presence of p -CA.

In Vitro Selective Antibacterial and Antiproliferative Effects of Ethanolic Extracts from Cambodian and Philippine Plants Used in Folk Medicine for Diarrhea Treatment

“…Asiatic acid, caffeic acid, p-coumaric acid, kaempferol, quercetin, rutin, and ursolic acid were isolated compounds with previously profound antiproliferative action to this cell line. In the study by Karakurt et al (2020), p-coumaric acid exhibited selective inhibition of Caco-2 and HT-29 cells compared to that of healthy colon epithelial cells (CCD-18Co). Since the decoction from the leaves of M. malabathricum L. is also traditionally consumed to treat diarrhea, we suggest a similar composition of bioactive compounds to be present in M. saigonense (Kuntze) Merr.…”

Upregulation of p53 by tannic acid treatment suppresses the proliferation of human colorectal carcinoma

“…SW620 and HT-29 cells were seeded into a 24-well plate and treated with 7.2 µmol L -1 and 37.6 µmol L -1 of TA, respectively for 48 h at 37 °C and 5 % CO 2 . The cells were harvested, counted with TC20 automated cell counter, and 5 × 10 3 of cells were transferred into a 6-well plate containing 1 % base agar as described in our previous study and incubated at 37 °C and 5 % CO 2 for 15 days (32). The colonies were then stained with 0.1 % toluidine blue and the number of colonies was counted and analyzed by Image J software.…”

New Insights Into the Anticancer Effects of p-Coumaric Acid: Focus on Colorectal Cancer

“… 5 Indeed, a growing body of evidence shows that western dietary pattern, with a predominance of high red meat and alcohol consumption at the expense of vegetable intake, is prospectively associated with CRC risk. 10 , 11 On the other hand, it has been suggested that adherence to the Mediterranean diet (MedDiet) is associated with a lower risk for cancers, including CRC. 12 Polyphenols are the most prevalent antioxidants among MedDiet nutraceuticals and have a wide variety of pharmacological actions such as anti-inflammatory and antitumorigenic properties.…”