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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

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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.

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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

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Acknowledgement

This work is supported in part by a fund from Council of scientific and Industrial research (CSIR) New Delhi. We thank Dr. Ramamurthy, Director, Ultrafast process laboratory, University of Madras for his help and advice in confocal imaging. The authors thank Prof. S. Niranjali and Prof. H. Devaraj, Department of Biochemistry and Biotechnology, respectively, University of Madras, for their helpful discussions in the doctoral committee meeting.

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  1. Department of Biochemistry, University of Madras, Guindy campus, Chennai, 600 025, Tamil nadu, India

    Ponnuraj Nagendraprabhu & Ganapasam Sudhandiran

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Correspondence to Ganapasam Sudhandiran.

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Nagendraprabhu, P., Sudhandiran, G. 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. Invest New Drugs 29, 207–224 (2011). https://doi.org/10.1007/s10637-009-9342-5

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