期刊
INVESTIGATIONAL NEW DRUGS
卷 29, 期 2, 页码 207-224出版社
SPRINGER
DOI: 10.1007/s10637-009-9342-5
关键词
Astaxanthin; Colon carcinogenesis; COX-2; NF-kappa B; ERK-2; Matrix metalloproteinase
资金
- Council of scientific and Industrial research (CSIR) New Delhi
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-kappa B-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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