Inhibition of cell proliferation and invasion in a human colon cancer cell line by 5-aminosalicylic acid.
BACKGROUND
5-Aminosalicylic acid lacks the well-known side effects associated with the long-term use of non-steroidal anti-inflammatory drugs. We investigated anti-carcinogenic mechanisms of 5-aminosalicylic acid on a colon cancer cell line.


METHODS
MTT analysis was performed for various colon cancer cell lines. The expression of NF-kappaB and metalloproteinases was examined in either HT-29 cells treated with IL-1beta and/or 5-aminosalicylic acid. Matrigel assay was used to evaluate invasive potential of HT-29 cells. Analysis of a cDNA microarray containing 8700 genes was performed to identify the alteration of gene expression in response to treatment to 5-aminosalicylic acid.


RESULTS
The use of MTT analysis showed that 5-aminosalicylic acid suppressed the growth of HT-29 cells. The activity of NF-kappaB was also decreased by combined-treatment with IL-1beta and 5-aminosalicylic acid. The use of an ELISA and zymography demonstrated that MMP-2 and MMP-9 enzyme activity were decreased in HT-29 cells by treatment with various concentration of 5-aminosalicylic acid. A matrigel analysis demonstrated that 5-aminosalicylic acid treatment on HT-29 significantly inhibited the invasiveness of the cells. In cDNA microarray, 163 genes following 5-aminosalicylic acid exposure showed altered expression.


CONCLUSIONS
This study indicated that 5-aminosalicylic acid suppresses the growth of human colon cancer cells and is able to inhibit MMPs expression via NF-kappaB mediated cell signals and invasiveness.
Kim
Y-H
YH
Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Kim
M H
MH
Kim
B J
BJ
Kim
J J
JJ
Chang
D K
DK
Son
H J
HJ
Rhee
P-L
PL
Rhee
J C
JC
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000201:enzymology / Q000473:pathology* / Q000517:prevention & control*; D015536:Down-Regulation / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D019073:HT29 Cells; D006801:Humans; D019804:Mesalamine / Q000008:administration & dosage*; D045726:Metalloproteases / Q000187:drug effects / Q000235:genetics; D016328:NF-kappa B / Q000187:drug effects; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D020411:Oligonucleotide Array Sequence Analysis
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016328:NF-kappa B; D019804:Mesalamine; D045726:Metalloproteases