Therapeutic potential of camel milk exosomes against HepaRG cells with potent apoptotic, anti-inflammatory, and anti-angiogenesis effects for colostrum exosomes - 09/10/21

Doi : 10.1016/j.biopha.2021.112220

Azza M. El-kattawy ^a, Ola Algezawy ^a, Mohammad Y. Alfaifi ^b, Enas A. Noseer ^c, Yousef M. Hawsawi ^d,^e, Othman R. Alzahrani ^f,^g, Abdulrahman Algarni ^h, Khaled A. Kahilo ^a, Mohammed A. El-Magd ^i,^⁎,^{^{1
ORCHID: 0000-0002-3314-9202}}
^a Department of Biochemistry, Faculty of Veterinary Medicine, Kafrelsheikh University, P.O. Box 33516, Kafrelsheikh, Egypt
^b Biology Department, Faculty of Science, King Khalid University, Abha 9004, Saudi Arabia
^c Department of Biochemistry, Faculty of Veterinary Medicine, Aswan University, Egypt
^d Research Center, King Faisal Specialist Hospital and Research Center, P.O. Box 40047, Jeddah 21499, Saudi Arabia
^e College of Medicine, Al-Faisal University, P.O. Box 50927, Riyadh 11533, Saudi Arabia
^f Genome and Biotechnology Unit, Faculty of Science, University of Tabuk, Tabuk, Saudi Arabia
^g Department of Biology, Faculty of Sciences, University of Tabuk, Tabuk, Saudi Arabia
^h Department of Biomedical Science, the Northern Border University, P.O.Box 1321, Arar, Saudi Arabia
ⁱ Department of Anatomy, Faculty of Veterinary Medicine, Kafrelsheikh University, P.O. Box 33516, Kafrelsheikh, Egypt

^⁎Corresponding author.

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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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Highlights

•	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.

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Keywords : Camel milk, Exosomes, HepaRG, Apoptosis, Inflammation, Angiogenesis

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Vol 143

Article 112220- novembre 2021 Retour au numéro

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Therapeutic potential of camel milk exosomes against HepaRG cells with potent apoptotic, anti-inflammatory, and anti-angiogenesis effects for colostrum exosomes - 09/10/21

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