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Author Babykutty, Suboj ♦ Suboj, Priya ♦ Srinivas, P. ♦ Nair, Asha S. ♦ Chandramohan, K. ♦ Gopala, S.
Source Sree Chitra Tirunal Institute for Medical Sciences & Technology
Content type Text
Publisher Clinical & Experimental Metastasis
File Format PDF
Language English
Subject Domain (in DDC) Natural sciences & mathematics ♦ Life sciences; biology ♦ Physiology & related subjects ♦ Biochemistry ♦ Technology ♦ Medicine & health
Subject Domain (in MeSH) Neoplasms ♦ Diseases ♦ Chemical Phenomena ♦ Cell Physiological Phenomena ♦ Biological Sciences
Subject Keyword Biochemistry
Abstract Nitric oxide (NO), an uncharged free radical is implicated in various physiological and pathological processes. The present study is an investigation on the effect of NO on proliferation, apoptosis and migration of colon cancer cells. Colon adenocarcinoma cells, WiDr, were used for the in vitro experiments. Tissues from colon adenocarcinoma, adjacent normal and inflammatory tissue and lymph node with metastasis were evaluated for iNOS, MMP-2/9 and Fra-1/Fra-2. NO increases the proliferation of cancer cells and simultaneously prevents apoptosis. Expression of MMP-2/9, RhoB and Rac-1 was enhanced by NO in a time dependent manner. Further, NO increased phosphorylation of ERK1/2 and induced nuclear translocation of Fra-1 and Fra-2. Electrophoretic mobility shift analysis and use of deletion mutant promoter constructs identified role of AP-1 in NO-mediated regulation of MMP-2/9. iNOS, MMP-2/9, Fra-1 and Fra-2 in normal and colon adenocarcinoma tissues were analyzed and it was found that increased expression of these proteins in cancer when compared to normal provides support to our in vitro findings. The study showed that the NO-cGMP-PKG promotes MMP-2/9 expression by activating ERK-1/2 and AP-1. This study reveals the insidious role of NO in imparting tumor aggressiveness.
Education Level UG and PG
Learning Resource Type Article
Educational Framework Medical Council of India (MCI)
Journal CLINICAL & EXPERIMENTAL METASTASIS
Volume Number 29
Issue Number 5
Page Count 22
Starting Page 471
Ending Page 492