Korashy Hesham M, El Gendy Mohamed A M, Alhaider Abdulqader A, El-Kadi Ayman O
Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, 11451 Riyadh, Saudi Arabia.
J Biomed Biotechnol. 2012;2012:782642. doi: 10.1155/2012/782642. Epub 2012 Feb 27.
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.
中东地区有一个传统观念，认为骆驼奶可能有助于预防和治疗多种癌症病例，然而，确切机制尚未得到研究。因此，我们检测了骆驼奶调节小鼠肝癌Hepa 1c1c7细胞系中一个著名的癌症激活基因细胞色素P450 1a1（Cyp1a1）以及癌症保护基因NAD(P)H：醌氧化还原酶1（Nqo1）和谷胱甘肽S-转移酶a1（Gsta1）表达的能力。我们的结果表明，骆驼奶以浓度依赖的方式在mRNA、蛋白质和活性水平上显著抑制了2,3,7,8-四氯二苯并对二恶英（TCDD，最有效的Cyp1a1诱导剂和已知致癌化学物质）对Cyp1a1基因表达的诱导。此外，骆驼奶显著降低了异源生物反应元件（XRE）依赖的荧光素酶活性，表明涉及转录机制。此外，骆驼奶的这种抑制作用与血红素加氧酶1的成比例增加有关。另一方面，骆驼奶以浓度依赖的方式显著诱导Nqo1和Gsta1 mRNA表达水平。RNA合成抑制剂放线菌素D完全阻断了骆驼奶对Nqo1 mRNA的诱导，表明需要通过转录机制进行从头RNA合成。总之，骆驼奶在转录和转录后水平上调节Cyp1a1、Nqo1和Gsta1的表达。
