1998 Abstract: SUPPRESSION OF ENDONUCLEASE EXPRESSION BY NONSTER-OIDAL ANTIINFLAMMATORY DRUGS (NSAID's) IN SPORADIC COLORECTAL CANCER. M. S. Kahlenberg, C. Volpe, D. L. Stoler, N. J. Petrelli, and G.R. Anderson. Division of Surgical Oncology and Dep't of Cellular and Molecular Biology, Roswell Park Cancer Institute, State University of NY, Buffalo, NY. 97
Abstracts 1998 Digestive Disease Week
#1001
SUPPRESSION OF ENDONUCLEASE EXPRESSION BY NONSTER-OIDAL ANTIINFLAMMATORY DRUGS (NSAID'S) IN SPORADIC COLORECTAL CANCER. M. S. Kahlenberg, C. Volpe, D. L. Stoler, N. J. Petrelli, and G.R. Anderson. Division of Surgical Oncology and Dep't of Cellular and Molecular Biology, Roswell Park Cancer Institute, State University of NY, Buffalo, NY.
The major form of genomic instability in sporadic colorectal cancer is dependent upon DNA break related processes. Endonucleases are responsible for cleaving DNA in normal molecular processes and are expressed in colorectal tumors. The effects of NSAID's on endonuclease expression in colorectal tumors was studied in order to further elucidate the mechanisms underlying NSAID's ability to decrease polyp formation and tumor recurrence. Methods: A colorectal tumor cell line (SW620) that constitutively expresses endonuclease was identified and adapted for growth in dialyzed fetal bovine serum. The tumor cells were then subjected to 3 different nonsteroidal agents; ASA, indomethacin, and ibuprofen at concentrations of 0.5, 1.0 and 2.0 mm. Media was changed daily and at 96 hrs, the cells were harvested and processed for proteins utilizing an SDS buffer. Endonuclease expression was determined by using zymographic analysis and the degree of expression as measured by densitometry was compared to SW620 control.
Results:
Suppression of Endonuclease Expression
ASA
Ibuprofen
Indomethacin
0.5 mm
21%
23%
7%
1.0 mm
26%
54%
5%
2.0 mm
43%
-
69%
Ibuprofen at 2.0 mm was toxic to SW620.
Conclusion: Administration of various NSAID's to a colorectal tumor cell line that constitutively expresses endonuclease results in a decreased expression of this enzyme. Endonuclease expression has been previously shown to be associated with enhanced genomic instability. NSAID administration decreases endonuclease expression and thus may serve to stabilize the genome. This may help to elucidate the mechanism behind the protective benefit of NSAID's in reducing polyp formation and colorectal cancer recurrence.
Copyright 1996 - 1998, SSAT, Inc. Revised 29 June 1998.
