Altered membrane lipid dynamics and chemoprevention by non-steroidal anti inflammatory drugs during colon carcinogenesis

The present work focuses on the anti-neoplastic role of non steroidal anti-inflammatory drugs (NSAIDs) in modulating the biophysical parameters of the colonic membranes in 1,2-dimethylhydrazine dihydrochloride (DMH) induced carcinogenesis. The steady-state fluores­ cence polarization technique was applied to assess membrane fluidity, membrane polarity and Iipid phase states. The decline in cholesterol content, biosynthesis and cholesterol: phospholipids ratio with DMH treat­ ment indicates more fluidity associated with carcinogen­ esis. The DMH group had shown lower order parameter indicating more fluidity whereas NSAIDs resulted in increasing the membrane Iipid order. The converging effects of these changes were more in membrane phase separations and membrane phase state. In DMH treat­ ment membrane shows les ser phase separation or high polarity, and more Iiquid crystalline state while for NSAID groups membranes ha ve higher phase separa­ tions or low polarity, and more ofthe gel phase. Further, NSAIDs induced anti-proliferative effects were evidently observed by apoptosis in the colonocytes by using acri­ dine orange-ethidium bromide fluorescent staining and Terminal de-oxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The results suggest that NSAIDs induced alteration in the membrane biophysical parame­ ters may be an important initiating event for the chemo­ preventive action.