Antiproliferative Effects of Hop-derived Prenylflavonoids and Their Influence on the Efficacy of Oxaliplatine, 5-fluorouracil and Irinotecan in Human ColorectalC Cells.

Martin Ambrož,Petra Matoušková,Kateřina Lněničková,Lenka Skálová,Iva Boušová

doi:10.3390/nu11040879

Abstract

Beer, the most popular beverage containing hops, is also frequently consumed by cancer patients. Moreover, non-alcoholic beer, owing to its nutritional value and high content of biological active compounds, is sometimes recommended to patients by oncologists. However, the potential benefits and negatives have to date not been sufficiently evaluated. The present study was designed to examine the effects of four main hop-derived prenylflavonoids on the viability, reactive oxygen species (ROS) formation, activity of caspases, and efficiency of the chemotherapeutics 5-fluorouracil (5-FU), oxaliplatin (OxPt) and irinotecan (IRI) in colorectal cancer cell lines SW480, SW620 and CaCo-2. All the prenylflavonoids exerted substantial antiproliferative effects in all cell lines, with xanthohumol being the most effective (IC50 ranging from 3.6 to 7.3 µM). Isoxanthohumol increased ROS formation and the activity of caspases-3/7, but 6-prenylnaringenin and 8-prenylnaringenin exerted antioxidant properties. As 6-prenylnaringenin acted synergistically with IRI, its potential in combination therapy deserves further study. However, other prenylflavonoids acted antagonistically with all chemotherapeutics at least in one cell line. Therefore, consumption of beer during chemotherapy with 5-FU, OxPt and IRI should be avoided, as the prenylflavonoids in beer could decrease the efficacy of the treatment.

Highlights

Colorectal carcinoma (CRC) is the third most common cancer in men and the second in women worldwide
Fluoropyrimidines (e.g. 5-fluorouracil, capecitabine), irinotecan, oxaliplatin, and combinations of these drugs are used in CRC chemotherapy, with 5-fluorouracil being the cornerstone
(8-PN), naringenin (NAR), oxaliplatin (OxPt), 5-fluorouracil (5-FU), irinotecan (IRT), N-2-hydroxyethylpiperazine-N0 -2-ethanesulfonic acid (HEPES) buffer, phosphate-buffered saline (PBS), 3-[(3-Cholamidopropyl)dimethylammonio]-1-propanesulfonate hydrate (CHAPS), DL-dithiothreitol (DTT), and neutral red were purchased from Sigma–Aldrich (Prague, Czech Republic)

Summary

Introduction

Colorectal carcinoma (CRC) is the third most common cancer in men and the second in women worldwide. It represents the fourth leading cause of cancer deaths in the world [1]. Depending on its type and stage, there are several ways to treat CRC, including local and systemic therapies. While curative surgery remains the mainstay of treatment for early stage CRC, the therapy of patients with lymph node positive or the metastatic form of CRC is primarily based on cytotoxic chemotherapy or radiochemotherapy. In spite of advances in systemic therapy, treatment failure occurs in almost 90% of patients with metastatic cancer. Intrinsic or acquired resistance to chemotherapy is likely to be a cause of the Nutrients 2019, 11, 879; doi:10.3390/nu11040879 www.mdpi.com/journal/nutrients

Methods

Results

Conclusion