Abstract
This study aimed to evaluate and compare the therapeutic effect of camel milk exosomes derived from colostrum, early, mid, and late lactation periods on liver cancer HepaRG cells. These exosomes showed cytotoxicity on HepaRG while being safer on normal human liver THLE-2 cells. Among the four different isolated exosome groups, exosomes isolated from colostrum exhibited the highest apoptotic potential on HepaRG as indicated by highest DNA damage and upregulated expression of Bax and caspase3 expression, but with lowest Bcl2 expression. HepaRG-treated with colostrum-derived exosomes also exhibited the lowest expression of inflammation-related genes (TNFα, NFkB, TGFβ1, and Cox2) and the angiogenesis-related gene VEGF. Colostrum-derived exosomes had significantly higher expression of lactoferrin and kappa casein than other milk-derived exosomes. These results indicate that colostrum-derived exosomes have a more potent anti-cancer effect on HepaRG cells than exosomes derived from the early, mid, and lat lactation periods. This effect could be mediated through induction of apoptosis and inhibition of inflammation and angiogenesis. Therefore, these exosomes could be used as safe adjuvants/carriers to deliver chemotherapeutics and to potentiate their anticancer effect on liver cancer cells.
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•Colostrum exosomes induced higher apoptosis dependent cytotoxic effects on HepaRG.•Colostrum exosomes induced higher DNA damage, upregulation of Bax and caspase3 genes, and downregulation of Bcl2 gene.•They also exhibited lower expression of TNFα, NFkB, TGFβ1, Cox2 and VEGF•Colostrum exosomes had a significant higher expression of lactoferrin and kappa casein.