The Growth Inhibitory Potential and Antimetastatic Effect of Camel Urine on Breast Cancer Cells In Vitro and In Vivo

Romli, Firdaus; Abu, Nadiah; Khorshid, Faten; Najmuddin, Syed Umar Faruq Syed; Yeap, Swee Keong; Mohamad, Nurul Elyani; Hamid, Muhajir; Alitheen, Noorjahan Banu; Rahman, Nik Mohd Afizan Nik Abd

doi:10.1177/1534735416656051

Cited by 20 publications

(27 citation statements)

References 60 publications

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“…As expected, administration of camel milk and its exosomes significantly downregulated the expression of MMP9 and ICAM1 in tumor tissues with best improvement by exosomes. Consistent with our data, Romli et al 31 also reported lower levels of ICAM1 expression in tumor tissues of mice following administration of camel urine. Additionally, ICAM1 upregulation is correlated with metastatic and invasive ability of many cancer cells, including breast cancer.…”

Section: Discussionsupporting

confidence: 93%

“…This suggests that oxidative stress/antioxidant pathway may be involved in the inhibitory effects of camel milk and its exosomes on tumor progression. Consistent with this, camel urine (which also has been known to have anticancer activity) also decreased MDA levels and iNOS mRNA expression in tumor tissues of mice 31 and increased MDA levels in breast cancer patients. 32 iNOS and NO accelerate tumor growth and progression through induction of the angiogenesis and metastasis.…”

Section: Discussionsupporting

confidence: 68%

“…A similar anti-inflammatory effect was reported for camel urine on the tumor tissues induced by MCF7 cells injection in mice. 31 Comparing the constituents of camel milk and urine, it is possible that exosomes are the major players in this action as they are produced by nearly all cell subtypes and abundantly secreted in the milk and urine.…”

Section: Discussionmentioning

confidence: 99%

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

Badawy

El-Magd

AlSadrah³

2018

Integr Cancer Ther

125

117

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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.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 68%

Section: Discussionmentioning

confidence: 99%

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

Badawy

El-Magd

AlSadrah³

2018

Integr Cancer Ther

125

117

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“…In the early 20th century, a collection of anecdotal records, “The Water of Life: A treatise on urine therapy” came to be considered the founding document of the field 4,5 . Since cancer in many cases requires agents that induce life‐threatening side effects, the possibility that a simple substance such as one's own urine could serve as a cancer treatment sparked interest 6‐9 . However, the existing body of scientific literature does not describe the therapeutic role of any specific components in urine.…”

Section: Introductionmentioning

confidence: 99%

Loading‐induced antitumor capability of murine and human urine

Fan

Liu

et al. 2020

FASEB j.

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While urine has been considered as a useful bio‐fluid for health monitoring, its dynamic changes to physical activity are not well understood. We examined urine's possible antitumor capability in response to medium‐level, loading‐driven physical activity. Urine was collected from mice subjected to 5‐minute skeletal loading and human individuals before and after 30‐minute step aerobics. Six cancer cell lines (breast, prostate, and pancreas) and a mouse model of the mammary tumor were employed to evaluate the effect of urine. Compared to urine collected prior to loading, urine collected post‐activity decreased the cellular viability, proliferation, migration, and invasion of tumor cells, as well as tumor weight in the mammary fat pad. Detection of urinary volatile organic compounds and ELISA assays showed that the loading‐conditioned urine reduced cholesterol and elevated dopamine and melatonin. Immunohistochemical fluorescent images presented upregulation of the rate‐limiting enzymes for the production of dopamine and melatonin in the brain. Molecular analysis revealed that the antitumor effect was linked to the reduction in molecular vinculin‐linked molecular force as well as the downregulation of the Lrp5‐CSF1‐CD105 regulatory axis. Notably, the survival rate for the high expression levels of Lrp5, CSF1, and CD105 in tumor tissues was significantly lowered in the Cancer Genome Atlas database. Collectively, this study revealed that 5‐ or 10‐minute loading‐driven physical activity was sufficient to induce the striking antitumor effect by activating the neuronal signaling and repressing cholesterol synthesis. The result supported the dual role of loading‐conditioned urine as a potential tumor suppressor and a source of diagnostic biomarkers.

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“…Dromedary camels in most regions of Asia and Africa are used as pack animals and as a source of food for nomads and low income rural populations. Their unique ability to withstand harsh environmental conditions coupled with their medical benefits [ 5 – 8 ], make camels an ideal case for further studies.…”

Section: Introductionmentioning

confidence: 99%

Genetic variants analysis of three dromedary camels using whole genome sequencing data

et al. 2018

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Whole genome wide identification and annotation of genetic variations in camels is in its first steps. The aim of this study was the identification of genome wide variants, functional annotations of them and enrichment analysis of affected genes using whole genome sequencing data of three dromedary camels. The genomes of two Iranian female dromedary camels that mostly used to produce meat and milk were sequenced to 41.9-fold and 38.6-fold coverage. A total of 4,727,238 single-nucleotide polymorphisms (SNPs) and 692,908 indels (insertions and deletions) were found by mapping raw reads to the dromedary reference assembly (GenBank Accession: GCA_000767585.1). In-silico functional annotation of the discovered variants in under study samples revealed that most SNPs (2,305,738; 48.78%) and indels (339,756; 49.03%) were located in intergenic regions. A comparison of the identified SNPs with those of the African camel (BioProject Accession: PRJNA269274) indicated that they had 993,474 SNPs in common. We found 15,168 non-synonymous SNPs in the shared variants of the three camels that could affect gene function and protein structure. Obtained results revealed that there were 7085, 6271 and 4688 non-synonymous SNPs among the 3436, 3058 and 2882 genes in the specific gene sets of Yazd dromedary, Trod dromedary and African dromedary, respectively. The list of genes predicted to be affected by non-synonymous variants in different individuals was subjected to gene ontology (GO) enrichment analysis.

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The Growth Inhibitory Potential and Antimetastatic Effect of Camel Urine on Breast Cancer Cells In Vitro and In Vivo

Cited by 20 publications

References 60 publications

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

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

Loading‐induced antitumor capability of murine and human urine

Genetic variants analysis of three dromedary camels using whole genome sequencing data

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