Investigational New Drugs

, Volume 29, Issue 2, pp 207–224

Astaxanthin inhibits tumor invasion by decreasing extracellular matrix production and induces apoptosis in experimental rat colon carcinogenesis by modulating the expressions of ERK-2, NFkB and COX-2

PRECLINICAL STUDIES

DOI: 10.1007/s10637-009-9342-5

Cite this article as:
Nagendraprabhu, P. & Sudhandiran, G. Invest New Drugs (2011) 29: 207. doi:10.1007/s10637-009-9342-5

Summary

Colon cancer is the third most malignant neoplasm in the world and it remains an important cause of mortality in Asian and Western countries. Astaxanthin (AST), a major component of carotenoids possesses attractive remedial features. The purpose of this study is to investigate the possible mechanism of action of astaxanthin against 1, 2 dimethyl hydrazine (DMH)-induced rat colon carcinogenesis. Wistar male rats were randomized into five groups, group 1 were control rats, group 2 were rats that received AST (15 mg/kg body wt p.o. everyday), rats in group 3 were induced with DMH (40 mg/kg body wt, s.c.), DMH-induced rats in groups 4 and 5 were either pre or post initiated with AST, respectively as in group 2. DMH-induced rats exhibited elevated expressions of Nuclear factor kappa B-p65 (NF-κB-p65), Cyclooxygenase-2 (COX-2), Matrixmetallo proteinases (MMP) 2/9, Proliferating cell nuclear antigen (PCNA), and Extracellular signal-regulated kinase-2 (ERK-2) as confirmed by immunofluorescence. Further, Westernblot analysis of MMPs-2/9, ERK-2 and Protein kinase B (Akt) revealed increased expressions of these proteins in DMH-induced groups of rats. AST-treatment decreased the expressions of all these vital proteins, involved in colon carcinogenesis. The ability of AST to induce apoptosis in the colon of DMH-induced rats was confirmed by Annexin-V/PI staining in a confocal microscopy, DNA fragmentation analysis and expression of caspase-3 by Western blotting. In conclusion, astaxanthin exhibits anti-inflammatory and anti-cancer effects by inducing apoptosis in DMH-induced rat colon carcinogenesis by modulating the expressions of NFkB, COX-2, MMPs-2/9, Akt and ERK-2.

Keywords

Astaxanthin Colon carcinogenesis COX-2 NF-κB ERK-2, Matrix metalloproteinase 

Abbreviations

AST

Astaxanthin

DMH

Dimethyl hydrazine

COX-2

Cyclooxygenase-2

NF-κB

Nuclear factor- κB

MMP

Matrix Metalloproteinases

ERK-2

Extracellular signal-regulated kinase-2

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Ponnuraj Nagendraprabhu
    • 1
  • Ganapasam Sudhandiran
    • 1
  1. 1.Department of BiochemistryUniversity of MadrasChennaiIndia

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