We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Milk Exosomal miR-27b Worsen Endoplasmic Reticulum Stress Mediated Colorectal Cancer Cell Death.
- Authors
Martino, Elisa; Balestrieri, Anna; Mele, Luigi; Sardu, Celestino; Marfella, Raffaele; D'Onofrio, Nunzia; Campanile, Giuseppe; Balestrieri, Maria Luisa
- Abstract
The relationship between dietary constituents and the onset and prevention of colorectal cancer (CRC) is constantly growing. Recently, the antineoplastic profiles of milk and whey from Mediterranean buffalo (Bubalus bubalis) have been brought to attention. However, to date, compared to cow milk, the potential health benefits of buffalo milk exosome-miRNA are still little explored. In the present study, we profiled the exosomal miRNA from buffalo milk and investigated the possible anticancer effects in CRC cells, HCT116, and HT-29. Results indicated that buffalo milk exosomes contained higher levels of miR-27b, miR-15b, and miR-148a compared to cow milk. Mimic miR-27b transfection in CRC cells induced higher cytotoxic effects (p < 0.01) compared to miR-15b and miR-148a. Moreover, miR-27b overexpression in HCT116 and HT-29 cells (miR-27b+) induced apoptosis, mitochondrial reactive oxygen species (ROS), and lysosome accumulation. Exposure of miR-27b+ cells to the bioactive 3kDa milk extract aggravated the apoptosis rate (p < 0.01), mitochondrial stress (p < 0.01), and advanced endoplasmic reticulum (ER) stress (p < 0.01), via PERK/IRE1/XBP1 and CHOP protein modulation (p < 0.01). Moreover, GSK2606414, the ER-inhibitor (ER-i), decreased the apoptosis phenomenon and XBP1 and CHOP modulation in miR-27b+ cells treated with milk (p < 0.01 vs. miR-27b++Milk), suggesting the ER stress as a cell-death-aggravating mechanism. These results support the in vitro anticancer activity of 3kDa milk extract and unveil the contribution of miR-27b in the promising beneficial effect of buffalo milk in CRC prevention.
- Subjects
PHYSIOLOGICAL stress; EXOSOMES; LYSOSOMES; ENDOPLASMIC reticulum; MICRORNA; MILK; APOPTOSIS; COLORECTAL cancer; GENE expression; MITOCHONDRIA; CELLULAR signal transduction; DESCRIPTIVE statistics; REACTIVE oxygen species; CELL death
- Publication
Nutrients, 2022, Vol 14, Issue 23, p5081
- ISSN
2072-6643
- Publication type
Article
- DOI
10.3390/nu14235081