Therapeutic Effect of Camel Milk and Its Exosomes on MCF7 Cells In Vitro and In Vivo

Abstract

Background/Objectives: In the Middle East, people consume camel milk regularly as it is believed to improve immunity against diseases and decrease the risk for cancer. Recently, it was noted that most of the beneficial effects of milk come from their nanoparticles, especially exosomes. Herein, we evaluated the anticancer potential of camel milk and its exosomes on MCF7 breast cancer cells (in vitro and in vivo) and investigated the possible underlying molecular mechanism of action. Methods/Results: Administration of camel milk (orally) and its exosomes (orally and by local injection) decreased breast tumor progression as evident by (a) higher apoptosis (indicated by higher DNA fragmentation, caspase-3 activity, Bax gene expression, and lower Bcl2 gene expression), (b) remarkable inhibition of oxidative stress (decrease in MDA levels and iNOS gene expression); (c) induction of antioxidant status (increased activities of SOD, CAT, and GPX), (d) notable reduction in expression of inflammation-(IL1b, NFκB), angiogenesis-(VEGF) and metastasis-(MMP9, ICAM1) related genes; and (e) higher immune response (high number of CD+4, CD+8, NK1.1 T cells in spleen). Conclusions: Overall, administration of camel milk–derived exosomes showed better anticancer effect, but less immune response, than treatment by camel milk. Moreover, local injection of exosomes led to better improvement than oral administration. These findings suggest that camel milk and its exosomes have anticancer effect possibly through induction of apoptosis and inhibition of oxidative stress, inflammation, angiogenesis and metastasis in the tumor microenvironment. Thus, camel milk and its exosomes could be used as an anticancer agent for cancer treatment.

Milk MicroRNAs in Health and Disease

“…In the same way, in vitro (Admyre et al., ; Badawy et al., ; Martin et al., ; Pieters et al., ; Qin et al., ; Vashisht et al., ) and in vivo (Arntz et al., ) investigations have implicated milk EVs, alone or in combination with other drugs, in local and systemic inflammations (Admyre et al., ; Badawy et al., ; Vashisht et al., ), immune cell maturation (Pieters et al., ), and oxidative stress modulation (Martin et al., ; Qin et al., ). In certain models, milk EVs were anti‐inflammatory and able to prevent and diminish symptoms in two mouse models of rheumatoid arthritis (Arntz et al., ).…”

“…Milk EVs have been extensively studied for their biological functions upon consumption (Agrawal et al., ; Aqil et al., ; Aqil, Munagala, Jeyabalan, Agrawal, & Gupta, ; Arntz et al., ; Badawy, El‐Magd, & AlSadrah, ; Leiferman et al., ; Matsuda & Patel, ; Munagala, Aqil, Jeyabalan, & Gupta, ; Munagala et al., ; Oliveira et al., , 2017) and numerous studies have reported that milk EVs are bioaccessible (survive digestion; Benmoussa et al., ; Kahn et al., ; Liao et al., ; Rani et al., ; Shandilya, Rani, Onteru, & Singh, ; Vashisht, Rani, Onteru, & Singh, ) and bioavailable (Le Doare et al., ; Wang et al., ; Zempleni, ; Zempleni et al., ).…”

“…According to more than 30 studies, from different teams around the world, milk EVs resisted in vitro digestion (Benmoussa et al., ; Kahn et al., ; Liao et al., ; Rani et al., ; Shandilya et al., ; Vashisht et al., ) were internalized by recipient cells upon co‐incubation (Admyre et al., , 2008; Aqil et al., , ; Badawy et al., ; Golan‐Gerstl et al., ; Hock et al., ; Kahn et al., ; Liao et al., ; Maburutse, Park, Oh, & Kim, ; Martin et al., ; Matsuda & Patel, ; Mobley et al., ; Munagala et al., ; Naslund et al., ; Qin et al., ; Vashisht, Rani, Onteru, & Singh, ; Yu et al., ), transduced through the intestinal wall in vitro (Rani et al., ; Shandilya et al., ; Wolf et al., ), and were detected in animal models after ingestion (Manca et al., ; Munagala et al., ) or intravenous injection (Somiya, Yoshioka, & Ochiya, ).…”

“…Twenty‐one studies involving milk EVs from humans, rat, camels, and most often cow milks reported milk EVs bioactivity in vitro on cells (Admyre et al., ; Aqil et al., , ; Badawy et al., ; Golan‐Gerstl et al., ; Hock et al., ; Martin et al., ; Matsuda & Patel, ; Mobley et al., ; Munagala et al., ; Naslund et al., ; Qin et al., ; Vashisht et al., ; Yu et al., ) and in vivo in animal models (Agrawal et al., ; Aqil et al., , ; Badawy et al., ; Leiferman et al., ; Munagala et al., ; Munagala et al., ; Somiya et al., ).…”

“…Functionality of milk EVs has been explored following their intrinsic biological activity or their potential as drug carriers for cancer treatment (Agrawal et al., ; Aqil et al., , ; Badawy et al., ; Munagala et al., , ; Qin et al., ; Somiya et al., ), for the modulation of inflammation (Admyre et al., ; Arntz et al., ; Badawy et al., ; Martin et al., ; Vashisht et al., ), for gut, bone, and muscle development (Chen et al., ; Hock et al., ; Leiferman et al., ; Martin et al., ; Mobley et al., ; Oliveira et al., , ), bacterial proliferation (Yu et al., ), and in the prevention of HIV infection (Naslund et al., ).…”