Mandal Animesh, Bhatia Deepak, Bishayee Anupam
Cancer Therapeutics and Chemoprevention Group, Department of Pharmaceutical Sciences, College of Pharmacy, Northeast Ohio Medical University, Rootstown, OH 44272, USA.
Department of Pharmacogenomics, Bernard J. Dunn School of Pharmacy, Shenandoah University, Ashburn, VA 20147, USA.
Nutrients. 2017 Apr 28;9(5):436. doi: 10.3390/nu9050436.
Pomegranate ( L.), a nutrient-rich unique fruit, has been used for centuries for the prevention and treatment of various inflammation-driven diseases. Based on our previous study, a characterized pomegranate emulsion (PE) exhibited a striking inhibition of dimethylbenz(a)anthracene (DMBA)-initiated rat mammary tumorigenesis via antiproliferative and apoptosis-inducing mechanisms. The objective of the present work is to investigate the anti-inflammatory mechanism of action of PE during DMBA rat mammary carcinogenesis by evaluating the expression of cyclooxygenase-2 (COX-2), heat shock protein 90 (HSP90), nuclear factor-κB (NF-κB) and nuclear factor erythroid 2p45 (NF-E2)-related factor 2 (Nrf2). Mammary tumor samples were harvested from our previous chemopreventive study in which PE (0.2-5.0 g/kg) was found to reduce mammary tumorigenesis in a dose-dependent manner. The expressions of COX-2, HSP90, NF-κB, inhibitory κBα (IκBα) and Nrf2 were detected by immunohistochemical techniques. PE decreased the expression of COX-2 and HSP90, prevented the degradation of IκBα, hindered the translocation of NF-κB from cytosol to nucleus and increased the expression and nuclear translocation of Nrf2 during DMBA-induced mammary tumorigenesis. These findings, together with our previous results, indicate that PE-mediated prevention of DMBA-evoked mammary carcinogenesis may involve anti-inflammatory mechanisms through concurrent but differential regulation of two interrelated molecular pathways, namely NF-κB and Nrf2 signaling.
石榴（L.）是一种营养丰富的独特水果，几个世纪以来一直被用于预防和治疗各种炎症引发的疾病。基于我们之前的研究，一种经过表征的石榴乳液（PE）通过抗增殖和诱导凋亡机制对二甲基苯并（a）蒽（DMBA）引发的大鼠乳腺肿瘤发生表现出显著抑制作用。本研究的目的是通过评估环氧合酶-2（COX-2）、热休克蛋白90（HSP90）、核因子-κB（NF-κB）和核因子红系2p45（NF-E2）相关因子2（Nrf2）的表达，研究PE在DMBA诱导的大鼠乳腺致癌过程中的抗炎作用机制。从我们之前的化学预防研究中收集乳腺肿瘤样本，在该研究中发现PE（0.2 - 5.0 g/kg）以剂量依赖的方式降低乳腺肿瘤发生。通过免疫组织化学技术检测COX-2、HSP90、NF-κB、抑制性κBα（IκBα）和Nrf2的表达。在DMBA诱导的乳腺肿瘤发生过程中，PE降低了COX-2和HSP90的表达，阻止了IκBα的降解，阻碍了NF-κB从细胞质向细胞核的转位，并增加了Nrf2的表达和核转位。这些发现与我们之前的结果一起表明，PE介导的对DMBA诱发的乳腺致癌作用的预防可能涉及抗炎机制，通过同时但不同程度地调节两个相互关联的分子途径，即NF-κB和Nrf2信号通路。
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