Long term effect of curcumin in restoration of tumour suppressor p53 and phase-II antioxidant enzymes via activation of Nrf2 signalling and modulation of inflammation in prevention of cancer

• Published in: PloS one 2015-04, Vol.10 (4), p.e0124000
• Main Authors: Das, Laxmidhar, Vinayak, Manjula
• Format: Article
• Language: English
• Subjects: Activation; Angiogenesis; Animals; Anticarcinogenic Agents - pharmacology; Antioxidants; Antioxidants - metabolism; Apoptosis; Attenuation; Bearing; Biochemistry; Cancer; Carcinogenesis; Carcinogens; Cell cycle; Consensus Sequence; Curcumin; Curcumin - pharmacology; Cyclooxygenase 2 - genetics; Cyclooxygenase 2 - metabolism; Cyclooxygenase-2; Deoxyribonucleic acid; Development and progression; DNA; Enzymes; Gene expression; Genetic aspects; Glutathione Reductase - genetics; Glutathione Reductase - metabolism; Glutathione Transferase - genetics; Glutathione Transferase - metabolism; Glycolysis; Growth factors; Hepatocytes; Inflammation; Inflammation Mediators - metabolism; Inhibition; Laboratories; Liver; Liver - drug effects; Liver - metabolism; Lymphocytes T; Lymphoma; Lymphoma, T-Cell - drug therapy; Lymphoma, T-Cell - metabolism; Lymphoma, T-Cell - prevention & control; Male; Metabolites; Metastasis; Mice; Mice, Inbred AKR; Modulation; Molecular biology; NAD(P)H Dehydrogenase (Quinone) - genetics; NAD(P)H Dehydrogenase (Quinone) - metabolism; NF-E2-Related Factor 2 - genetics; NF-E2-Related Factor 2 - metabolism; Nitric oxide; Nitric Oxide Synthase Type II - genetics; Nitric Oxide Synthase Type II - metabolism; Nitric-oxide synthase; Non-Hodgkin's lymphomas; Oxidative stress; p53 Protein; Patient outcomes; Phytochemicals; Prevention; Protein Binding - drug effects; Proteins; Restoration; Risk factors; RNA, Messenger - genetics; RNA, Messenger - metabolism; Rodents; Signal transduction; Signal Transduction - drug effects; Signaling; Smooth muscle; T-cell lymphoma; Transforming Growth Factor beta1 - genetics; Transforming growth factors; Tumor microenvironment; Tumor Microenvironment - drug effects; Tumor proteins; Tumor Suppressor Protein p53 - metabolism; Tumors; Zoology
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0124000

Inhibition of carcinogenesis may be a consequence of attenuation of oxidative stress via activation of antioxidant defence system, restoration and stabilization of tumour suppressor proteins along with modulation of inflammatory mediators. Previously we have delineated significant role of curcumin during its long term effect in regulation of glycolytic pathway and angiogenesis, which in turn results in prevention of cancer via modulation of stress activated genes. Present study was designed to investigate long term effect of curcumin in regulation of Nrf2 mediated phase-II antioxidant enzymes, tumour suppressor p53 and inflammation under oxidative tumour microenvironment in liver of T-cell lymphoma bearing mice. Inhibition of Nrf2 signalling observed during lymphoma progression, resulted in down regulation of phase II antioxidant enzymes, p53 as well as activation of inflammatory signals. Curcumin potentiated significant increase in Nrf2 activation. It restored activity of phase-II antioxidant enzymes like GST, GR, NQO1, and tumour suppressor p53 level. In addition, curcumin modulated inflammation via upregulation of TGF-β and reciprocal regulation of iNOS and COX2. The study suggests that during long term effect, curcumin leads to prevention of cancer by inducing phase-II antioxidant enzymes via activation of Nrf2 signalling, restoration of tumour suppressor p53 and modulation of inflammatory mediators like iNOS and COX2 in liver of lymphoma bearing mice.