Effect of allyl isothiocyanate on NF-κB signaling in 7,12-dimethylbenz(a)anthracene and N-methyl-N-nitrosourea-induced mammary carcinogenesis. 2018

Thangarasu Rajakumar, and Pachaiappan Pugalendhi, and Rajendran Jayaganesh, and Dhanabalan Ananthakrishnan, and Krishnaswamy Gunasekaran
Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar, Tamil Nadu, 608 002, India.

BACKGROUND Inflammation plays a pivotal role in the process of carcinogenesis and phytochemicals have anti-inflammatory properties gaining more importance in cancer chemoprevention. The present study aimed to investigate the anti-inflammatory effect of allyl isothiocyanate (AITC) on 7,12-dimethylbenz(a)anthracene (DMBA)- and N-methyl-N-nitrosourea (MNU)-induced mammary carcinogenesis in female Sprague-Dawley rats. METHODS RT-PCR and western blot analysis showed that inflammatory markers such as NF-κB p65, TNF-α, and IL-6 were overexpressed in mammary tumor tissues. Histological analysis of tumor tissues shows abnormality in hematoxylin and eosin (H&E) staining and toluidine blue (TB) staining of mast cell content, and lipid accumulation in oil red O staining. RESULTS Administration of AITC (20 mg/kg bw) to carcinogen-injected rats significantly decreased the expression of NF-κB p65, TNF-α, and IL-6 in mammary tissues. Further, molecular docking study demonstrates the binding of AITC to NF-κB p65. Remarkably, AITC treatments control the growth of cancer cells as clearly evidenced by histopathological analysis. Staining of mammary tissues for mast cells and lipids indicates that AITC treatment to carcinogen-administrated rats significantly reduced mammary tumorigenesis. CONCLUSIONS The result suggests that AITC has anti-inflammatory potential to prevent DMBA- and MNU-induced mammary carcinogenesis in rats.

UI MeSH Term Description Entries
D008325 Mammary Neoplasms, Experimental Experimentally induced mammary neoplasms in animals to provide a model for studying human BREAST NEOPLASMS. Experimental Mammary Neoplasms,Neoplasms, Experimental Mammary,Experimental Mammary Neoplasm,Mammary Neoplasm, Experimental,Neoplasm, Experimental Mammary
D008770 Methylnitrosourea A nitrosourea compound with alkylating, carcinogenic, and mutagenic properties. Nitrosomethylurea,N-Methyl-N-nitrosourea,NSC-23909,N Methyl N nitrosourea,NSC 23909,NSC23909
D002273 Carcinogens Substances that increase the risk of NEOPLASMS in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. Carcinogen,Oncogen,Oncogens,Tumor Initiator,Tumor Initiators,Tumor Promoter,Tumor Promoters,Initiator, Tumor,Initiators, Tumor,Promoter, Tumor,Promoters, Tumor
D005260 Female Females
D005520 Food Preservatives Substances capable of inhibiting, retarding or arresting the process of fermentation, acidification or other deterioration of foods. Preservatives, Food
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D015127 9,10-Dimethyl-1,2-benzanthracene Polycyclic aromatic hydrocarbon found in tobacco smoke that is a potent carcinogen. 7,12-Dimethylbenzanthracene,7,12-Dimethylbenz(a)anthracene,7,12 Dimethylbenzanthracene
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D015972 Gene Expression Regulation, Neoplastic Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue. Neoplastic Gene Expression Regulation,Regulation of Gene Expression, Neoplastic,Regulation, Gene Expression, Neoplastic
D016328 NF-kappa B Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA. Immunoglobulin Enhancer-Binding Protein,NF-kappa B Complex,Nuclear Factor kappa B,Transcription Factor NF-kB,kappa B Enhancer Binding Protein,Ig-EBP-1,NF-kB,NF-kappaB,Nuclear Factor-Kappab,Complex, NF-kappa B,Enhancer-Binding Protein, Immunoglobulin,Factor NF-kB, Transcription,Factor-Kappab, Nuclear,Ig EBP 1,Immunoglobulin Enhancer Binding Protein,NF kB,NF kappa B Complex,NF kappaB,NF-kB, Transcription Factor,Nuclear Factor Kappab,Transcription Factor NF kB

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