Abstract
There is a traditional belief in the Middle East that camel milk may aid in prevention and treatment of numerous cases of cancer yet, the exact mechanism was not investigated. Therefore, we examined the ability of camel milk to modulate the expression of a well-known cancer-activating gene, Cytochrome P450 1a1 (Cyp1a1), and cancer-protective genes, NAD(P)H:quinone oxidoreductase 1 (Nqo1) and glutathione S-transferase a1 (Gsta1), in murine hepatoma Hepa 1c1c7 cell line. Our results showed that camel milk significantly inhibited the induction of Cyp1a1 gene expression by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the most potent Cyp1a1 inducer and known carcinogenic chemical, at mRNA, protein, and activity levels in a concentration-dependent manner. In addition, camel milk significantly decreased the xenobiotic responsive element (XRE)-dependent luciferase activity, suggesting a transcriptional mechanism is involved. Furthermore, this inhibitory effect of camel milk was associated with a proportional increase in heme oxygenase 1. On the other hand, camel milk significantly induced Nqo1 and Gsta1 mRNA expression level in a concentration-dependent fashion. The RNA synthesis inhibitor, actinomycin D, completely blocked the induction of Nqo1 mRNA by camel milk suggesting the requirement of de novo RNA synthesis through a transcriptional mechanism. In conclusion, camel milk modulates the expression of Cyp1a1, Nqo1, and Gsta1 at the transcriptional and posttranscriptional levels.
Highlights
The aryl hydrocarbon receptor (AhR), a cytosolic ligandactivated transcriptional factor, belongs to the basic-helixloop-helix/Per-AhR nuclear translocator (ARNT)-Sim (PAS) family of transcription proteins, which are involved in regulation of cell differentiation and proliferation [1, 2]
The current study provides the first mechanistic evidence of the ability of camel milk to significantly inhibit the induction of Cytochrome P450 1a1 (Cyp1a1), a cancer-activating gene, and to induce NAD(P)H:quinone oxidoreductase 1 (Nqo1) and glutathione S-transferase a1 (Gsta1), cancer protecting genes in Hepa 1c1c7 cells at the transcriptional and posttranscriptional levels
We hypothesize that camel milk exhibits anticancer effects by inhibiting the expression of Cyp1a1 and/or inducing Nqo1 and Gsta1 genes
Summary
The aryl hydrocarbon receptor (AhR), a cytosolic ligandactivated transcriptional factor, belongs to the basic-helixloop-helix (bHLH)/Per-ARNT-Sim (PAS) family of transcription proteins, which are involved in regulation of cell differentiation and proliferation [1, 2]. The AhR-regulated gene batteries include phase I xenobiotic metabolizing enzymes such as the cytochrome P450 1A1 (CYP1A1), CYP1A2, CYP1B1 and phase II enzymes such as NAD(P)H:quinone oxidoreductase 1 (NQO1), glutathione S-transferase A1 (GSTA1), uridine diphosphate glucuronosyltransferase 1A6, and aldehyde dehydrogenase-3 [3, 4]. Among these genes, CYP1A1 plays a particular role in bioactivating procarcinogens into carcinogen and toxic
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