Mandal Animesh, Bishayee Anupam
Cancer Therapeutics and Chemoprevention Group, Department of Pharmaceutical Sciences, College of Pharmacy, Northeast Ohio Medical University, Rootstown, OH 44272, USA.
Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, California Northstate University, Elk Grove, CA 95757, USA.
Int J Mol Sci. 2015 Jan 22;16(2):2426-45. doi: 10.3390/ijms16022426.
Trianthema portulacastrum, a medicinal and dietary plant, has gained substantial importance due to its various pharmacological properties, including anti-inflammatory and anticarcinogenic activities. We have recently reported that a characterized T. portulacastrum extract (TPE) affords a considerable chemoprevention of 7,12-dimethylbenz(a)anthracene (DMBA)-induced rat mammary tumorigenesis though the underlying mechanisms are not completely understood. The objective of this study was to investigate anti-inflammatory mechanisms of TPE during DMBA mammary carcinogenesis in rats by monitoring cyclooxygenase-2 (COX-2), heat shock protein 90 (HSP90), nuclear factor-kappaB (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf2). Mammary tumors were harvested from our previous study in which TPE (50-200 mg/kg) was found to inhibit mammary tumorigenesis in a dose-response manner. The expressions of intratumor COX-2, HSP90, NF-κB, inhibitory kappaB-alpha (IκBα) and Nrf2 were determined by immunohistochemistry. TPE downregulated the expression of COX-2 and HSP90, blocked the degradation of IκBα, hampered the translocation of NF-κB from cytosol to nucleus and upregulated the expression and nuclear translocation of Nrf2 during DMBA mammary carcinogenesis. These results in conjunction with our previous findings suggest that TPE prevents DMBA-induced breast neoplasia by anti-inflammatory mechanisms mediated through simultaneous and differential modulation of two interconnected molecular circuits, namely NF-κB and Nrf2 signaling pathways.
松叶牡丹，一种药食两用植物，因其多种药理特性，包括抗炎和抗癌活性，而变得极为重要。我们最近报道，一种经过表征的松叶牡丹提取物（TPE）对7,12-二甲基苯并(a)蒽（DMBA）诱导的大鼠乳腺肿瘤发生具有显著的化学预防作用，尽管其潜在机制尚未完全明确。本研究的目的是通过监测环氧合酶-2（COX-2）、热休克蛋白90（HSP90）、核因子-κB（NF-κB）和核因子红细胞2相关因子2（Nrf2），来探究TPE在大鼠DMBA乳腺致癌过程中的抗炎机制。乳腺肿瘤取自我们之前的研究，在该研究中发现TPE（50 - 200 mg/kg）以剂量反应方式抑制乳腺肿瘤发生。通过免疫组织化学法测定肿瘤内COX-2、HSP90、NF-κB、抑制性κB-α（IκBα）和Nrf2的表达。在DMBA乳腺致癌过程中，TPE下调COX-2和HSP90的表达，阻断IκBα的降解，阻碍NF-κB从细胞质向细胞核的转位，并上调Nrf2的表达和核转位。这些结果与我们之前的发现共同表明，TPE通过同时和差异性调节两个相互关联的分子回路，即NF-κB和Nrf2信号通路介导的抗炎机制，预防DMBA诱导的乳腺肿瘤形成。
