[Effect of phospholipase C inhibitor peptides on cancer cell growth].
We analyzed the effect of PLC inhibitor (PCI) peptides in their growth and cell cycle. N-Myristoylated PCI peptide, myr-PCI, originally developed based on the PCI sequence of PLC-gamma 2, inhibited activity of purified PLC isoforms in vitro. When myr-PCI was added to KMS-4 and KMS-8 cells, both derived from familial adenomatous polyposis patients, it suppressed the production of inositol trisphosphate, DNA synthesis, and cell growth, all of which were induced by serum in both KMS 4 and KMS 8 cells. Flow cytometry analysis with propidium iodide labelling revealed marked decreases in the percentage of KMS 8 cells in S phase and increases in G0, G1 by the addition of myr PCI. These results indicate that the activation of PLC is essential for growth and transformed properties of these colorectal carcinoma cells, and also that PLC inhibitors could be an anti-tumor drug for some cases.
Homma
M
M
Dept. of Hygiene and Oncology, Tokyo Medical and Dental University School of Medicine.
Homma
Y
Y
D011125:Adenomatous Polyposis Coli / Q000378:metabolism / Q000473:pathology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004273:DNA, Neoplasm / Q000096:biosynthesis / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D014407:Tumor Cells, Cultured / Q000187:drug effects; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors*
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D004791:Enzyme Inhibitors; D010738:Type C Phospholipases