Antibacterial, Antifungal, and Anticancer Effects of Camel Milk Exosomes: An In Vitro Study

SIMPLE SUMMARY: Camel milk (CM) and its exosomes (CM-EXO) have many health-promoting effects due to their antibacterial, antifungal, and anticancer effects. Herein, we investigated the CM-EXO antimicrobial effect on Gram-positive bacteria (Staphylococcus aureus, Micrococcus luteus, and Enterococcus feacalis), Gram-negative strains (Escherichia coli, Pseudomonas aeruginosa, and Proteus mirabilis), and Candida albicans and found only bacteriostatic effects against Gram-negative strains, and fungistatic effect. To the best of our knowledge, this is the first study to report a selective apoptotic effect of CM-EXOs on HepG2 and CaCo2 cells, but not on normal Vero cells. CM-EXOs also induced the elevation of intracellular reactive oxygen species and reduced antioxidant status in cancer cells but not in normal cells. ABSTRACT: Camel milk (CM) has potent antibacterial and antifungal effects and camel milk exosomes (CM-EXO) have been shown to inhibit the proliferation of a large variety of cancer cells including HepaRG, MCF7, Hl60, and PANC1. However, little is known regarding the effects of CM-EXO on bacteria, fungi, HepG2, CaCo2, and Vero cells. Therefore, this study aimed to evaluate the antibacterial, antifungal, and anticancer effects of CM-EXO. EXOs were isolated from CM by ultracentrifugation and characterized by transmission electron microscope and flow cytometry. Unlike CM, CM-EXO (6 mg/mL) had no bactericidal effects on Gram-positive bacteria (Staphylococcus aureus, Micrococcus luteus, and Enterococcus feacalis) but they had bacteriostatic effects, especially against Gram-negative strains (Escherichia coli, Pseudomonas aeruginosa, and Proteus mirabilis), and fungistatic effects on Candida albicans. HepG2, CaCo2, and Vero cells were respectively treated with CM-EXOs at low (6.17, 3.60, 75.35 μg/mL), moderate (12.34, 7.20, 150.70 μg/mL), and high (24.68, 14.40, 301.40 μg/mL) doses and the results revealed that CM-EXOs triggered apoptosis in HepG2 and CaCo2 cells, but not in normal Vero cells, as revealed by high Bax expression and caspase 3 activities and lower expression of Bcl2. Interestingly, CM-EXOs also induced the elevation of intracellular reactive oxygen species and downregulated the expression of antioxidant-related genes (NrF2 and HO-1) in cancer cells but not in normal cells. CM-EXOs have antibacterial and antifungal effects as well as a selective anticancer effect against HepG2 and CaCo2 cells with a higher safety margin on normal cells.