[Inhibitory effect of 5-aminoisoquinolinone on PARP activity in colon carcinoma cell line HT-29].
OBJECTIVE
5-Aminoisoquinolinone(5-AIQ),a poly(adenosine 5'-diphosphate ribose) polymerase (PARP) inhibitor, plays an important role in inflammation, but its role in tumors is unclear. This study was to investigate the biological role of 5-AIQ-induced PARP inhibition in colon carcinoma cell line HT-29.


METHODS
The expression of poly(adenosine 5'-diphosphate ribose) (PAR) and co-expression of PAR with P-selectin and intercellular adhesion molecule-1 (ICAM-1) in 45 specimens of colorectal carcinoma and 10 specimens of adjacent normal colorectal mucosa were detected by SP immunohistochemistry and double immunofluorescence staining. After treatment of 5-AIQ, the adhesion of colon carcinoma cell line HT-29 to human umbilical vein endothelial cells (HUVEC) was detected by adhesion experimentû the expression of PAR, P-selectin, and ICAM-1 in HT-29 cells was detected by SP immunohistochemistry.


RESULTS
The positive rate of PAR was significantly higher in colorectal carcinoma than in control colorectal mucosa (77.8% vs. 10.0%, P < 0.05), and higher in colorectal carcinomas with metastasis than in colorectal carcinomas without metastasis (86.7% vs. 60.0%). PAR expression was correlated to P-selectin and ICAM-1 expression. Cell adhesion rate was significantly lower in 100, 300, and 500 mumol/L 5-AIQ-treated HT-29 cells than in control cells (55.79%, 46.31%, and 39.77% vs. 100%, P < 0.05). The protein levels of PAR, P-selectin, and ICAM-1 were significantly lower in 5-AIQ-treated HT-29 cells than in control cells (1.41+/-0.12 vs. 2.61+/-0.10, 1.57+/-0.13 vs. 2.73+/-0.16, 1.23+/-0.13 vs. 2.30+/-0.12, P < 0.05).


CONCLUSIONS
PARP activity is enhanced in colorectal carcinoma. PARP inhibitor 5-AIQ can inhibit the adhesion of HT-29 cells to HUVECs, and the expression of PAR, P-selectin, and ICAM-1 in HT-29 cells.
Hao
Lan-Xiang
LX
Department of Pathology,Chongqing Medical University, Chongqing, 400016, P. R. China.
Wang
Ya-Lan
YL
Cai
Li
L
Li
Yuan-Yuan
YY
D002448:Cell Adhesion / Q000187:drug effects*; D002478:Cells, Cultured; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D019073:HT29 Cells / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007546:Isoquinolines / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D019007:P-Selectin / Q000378:metabolism; D000071137:Poly (ADP-Ribose) Polymerase-1; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D012004:Rectal Neoplasms / Q000378:metabolism / Q000473:pathology; D014471:Umbilical Veins / Q000166:cytology
C411425:5-aminoisoquinolinone; D007546:Isoquinolines; D019007:P-Selectin; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D018799:Intercellular Adhesion Molecule-1; D011064:Poly Adenosine Diphosphate Ribose; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases