Delivery of polyphenol-rich plant extracts using lactose-free whey permeate: cytotoxic and mitochondrial effects in Caco-2 cells.
TL;DR
Investigating the biological activity of polyphenol-rich plant extracts incorporated into a lactose-free WP matrix on human colorectal adenocarcinoma Caco-2 cells suggests that lactose-free WP model can serve as a potential food-compatible matrix for polyphenol-rich extracts, enabling cytotoxic effects on tumor cells, possibly with mitochondrial involvement.
Abstract
The development of functional food matrices for the delivery of bioactive compounds, together with the valorization of agro-industrial by-products, is a growing research area. Whey permeate (WP), an abundant dairy by-product suitable for human consumption, has attracted interest as a potential food-compatible matrix, although its use for incorporating bioactive compounds remains limited. This study investigated the biological activity of polyphenol-rich plant extracts incorporated into a lactose-free WP matrix on human colorectal adenocarcinoma Caco-2 cells. Extracts from peanut skin (Arachis hypogaea L.), Marcela del campo (Achyrocline satureioides (Lam.) D.C.), and yerba mate (Ilex paraguariensis A. St. Hil) were evaluated. Cytotoxicity (CC50) was determined in Caco-2 and non-tumor Vero cells by Neutral Red uptake and Resazurin reduction assays. WP-based formulations exhibited cytotoxic activity against tumor cells, with CC50 values ranging from 15.9 to 28.5 mg/mL of dairy carbohydrates and from 124 to 223 μg/mL of plant extracts, while preserving viability in non-tumor cells. Mechanistic analyses showed increased superoxide anion generation (121.88-139.82% of cell control), loss of mitochondrial membrane potential (53.9-74.7% of cell control), and ultrastructural mitochondrial damage, with the strongest effects observed with WP and peanut skin extract. These findings suggest that lactose-free WP model can serve as a potential food-compatible matrix for polyphenol-rich extracts, enabling cytotoxic effects on tumor cells, possibly with mitochondrial involvement. This approach provides a basis for further investigation of WP systems and support the valorization of dairy and peanut by-products for future food applications.