Trianthema portulacastrum Linn. displays anti-inflammatory responses during chemically induced rat mammary tumorigenesis through simultaneous and differential regulation of NF-kappaB and Nrf2 signaling pathways.

Trianthema portulacastrum Linn. displays anti-inflammatory responses during chemically induced rat mammary tumorigenesis through simultaneous and differential regulation of NF-kappaB and Nrf2 signaling pathways.

Mandal Animesh; Bishayee Anupam

International journal of molecular sciences

2015

2015-01

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-kappaB) 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-kappaB, inhibitory kappaB-alpha (IkappaBalpha) and Nrf2 were determined by immunohistochemistry. TPE downregulated the expression of COX-2 and HSP90, blocked the degradation of IkappaBalpha, hampered the translocation of NF-kappaB 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-kappaB and Nrf2 signaling pathways.

Female; Animals; Signal Transduction/*drug effects; Immunohistochemistry; Rats; Up-Regulation/drug effects; NF-kappa B/*metabolism; Aizoaceae/*chemistry/metabolism; Anti-Inflammatory Agents/chemistry/isolation & purification/*pharmacology; Breast Neoplasms/chemically induced/metabolism/pathology; Cyclooxygenase 2/metabolism; HSP90 Heat-Shock Proteins/metabolism; NF-E2-Related Factor 2/*metabolism; Plant Extracts/chemistry; Sprague-Dawley; 10-Dimethyl-1; 9; Plant Components; 2-benzanthracene/toxicity; Aerial/chemistry/metabolism

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