Modulation of differentiation-related responses in human colon carcinoma cells by protein kinase inhibitor H-7.
1-(isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7), a potent inhibitor of protein kinases, has been used as a tool to examine the role of protein kinases in a variety of cellular functions. Contingent on the cell type, H-7 has been reported either to inhibit or to promote differentiation. The biological effects of H-7 on human colon adenocarcinoma cells have not been reported. In this study we investigated the effects of H-7 on differentiation - related parameters such as cellular morphology, proliferation, the expression of carcinoembryonic antigen (CEA), fibronectin and cytokeratins in human adenocarcinoma cell lines HCT116 and SW480. H-7 induced pronounced morphological alterations in both cell lines. It induced fibronectin expression and down-modulated CEA expression and secretion in the SW480 cells, but not in the HCT116 cells. Expression of acidic keratins was not affected by H-7 treatment in both cell lines. However, the expression of basic keratins were down-modulated in the HCT116 cells and enhanced in the SW480 cells. These studies showed that the protein kinase inhibitor, H-7, modulated phenotypic properties in human colon adenocarcinoma cells. Alterations in phenotypic properties and their significance in regard to the induction of differentiation are discussed.
Chakrabarty
S
S
Pharmaceutical Research Institute, Bristol-Myers Squibb Company, Wallingford, CT 06492-7660.
Chen
J W
JW
Chen
X Y
XY
Trujillo
J M
JM
Lin
P F
PF
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000230:Adenocarcinoma / Q000737:chemistry / Q000473:pathology*; D002272:Carcinoembryonic Antigen / Q000032:analysis; D002454:Cell Differentiation; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000737:chemistry / Q000473:pathology*; D005353:Fibronectins / Q000032:analysis; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology*; D007633:Keratins / Q000032:analysis; D010879:Piperazines / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors
D002272:Carcinoembryonic Antigen; D005353:Fibronectins; D007546:Isoquinolines; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D007633:Keratins; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine