The Comparative Role of BAMLET and 5-Fluorouracil in Colorectal Cancer Cells by Targeting WNT/β-Catenin Pathway

Abstract

Background: Aberrant activation of the WNT/β-catenin signaling pathway is involved in various types of cancers, particularly colorectal cancer (CRC), which is a prevalent malignancy. Targeting the Wnt signaling pathway has gained a reputation as an attractive therapeutic strategy, mainly because of its potential for regulating cell proliferation, migration, differentiation, angiogenesis, and apoptosis. Objectives: The aim of the current research was to investigate the effects of 5-Fluorouracil (5-FU) and bovine alpha-lactalbumin made lethal to tumor cells (BAMLET), a complex of oleic acid with bovine α-lactalbumin protein, on colon cancer cells focusing on the Wnt signaling pathway. Methods: For this purpose, HT-29 and HCT116 cells were treated with 5-FU and BAMLET, and the expression levels of Wnt signaling-related proteins (β-catenin and E-cadherin) and VEGF as angiogenesis regulators were evaluated by quantitative real-time polymerase chain reaction (RT-qPCR) and Western Blot analysis. Results: Bovine alpha-lactalbumin made lethal to tumor cells treatment down-regulated the expression of β-catenin and up-regulated the expression of E-cadherin significantly compared to the 5-FU (P < 0.0001). The reduced mRNA levels of VEGF in treated cells revealed the effectiveness of 5-FU and BAMLET on angiogenesis. Conclusions: Bovine alpha-lactalbumin made lethal to tumor cells can be considered for targeting the Wnt signaling pathway and angiogenesis. It is amenable to further investigation in the development of CRC treatment.