Chemopreventive allylthiopyridazines inhibit invasion, migration and angiogenesis in hepatocarcinoma cells.
Numerous studies have revealed the chemopreventive and hepatoprotective activities of dietary and synthetic organosulfur compounds. We previously showed that synthetic allylthiopyridazine derivatives, designated as K compounds, induced apoptosis in SK-Hep-1 hepatocarcinoma cells. In order to extend our program to pursue the chemopreventive potential of these compounds, we investigated the effects of the K compounds on invasive and migrative properties of the SK-Hep-1 cells in this study. Here, we show that 3-methoxy-6-allylthiopyridazine (K6) and 3-propoxy-6-allylthiopyridazine (K17) efficiently inhibit SK-Hep-1 cell invasion and migration. A prominent downregulation of matrix metalloproteinase (MMP)-2, but not MMP-9, was observed, presenting MMP-2 as a potential target molecule for the anti-invasive and anti-migrative activities of the compounds. Since hepatocarcinoma is characterized as a hypervascular tumor, we examined the effect of the compounds on angiogenesis of human umbilical vein endothelial cells (HUVECs). The K compounds exerted anti-angiogenic activity, supporting that the development of these compounds would be a promising approach for treatment of hepatocarcinoma. Taken in conjunction with the fact that hepatocellular carcinoma is one of the most lethal malignancies, our findings may be critical to the chemopreventive potential of these synthetic organosulfur compounds for hepatocarcinoma.
Lee
Eun-Jung
EJ
College of Pharmacy, Duksung Women's University, Seoul 132-714, Korea.
Shin
Ilchung
I
Kwon
Soon-Kyoung
SK
Shin
Hea-Soon
HS
Moon
Aree
A
D016588:Anticarcinogenic Agents / Q000494:pharmacology; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004730:Endothelium, Vascular / Q000166:cytology; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008956:Models, Chemical; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic; D011724:Pyridazines / Q000494:pharmacology*; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D013997:Time Factors; D014471:Umbilical Veins / Q000166:cytology; D014945:Wound Healing
D016588:Anticarcinogenic Agents; D011724:Pyridazines; D013778:Tetrazolium Salts; D013844:Thiazoles; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C022616:thiazolyl blue