TPA induces transglutaminase C and inhibits cell growth in the colon carcinoma cell line SW620.
In contrast to most other systems, TPA induced TGc activity and protein in SW620 human colon carcinoma cells. This induction was accompanied by cell growth inhibition and increased apoptosis. The general protein kinase-C inhibitor GF-109203X blocked the induction of TGc by TPA, whereas the specific inhibitor of the PKC alpha isoform, the indocarbazole Go6976, reduced it by 40%. These PKC inhibitors had similar inhibitory effects on TPA increased apoptosis and inhibition of cell growth, suggesting that the observed actions of TPA are mediated by PKC, and a close connection between TGc activity, increased apoptosis and cell growth inhibition. We conclude that TPA may offer new approaches in the management of colon cancer cell growth.
Kósa
K
K
Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, Maryland 20892-4255, USA.
Rosenberg
M I
MI
Chiantore
M V
MV
De Luca
L M
LM
D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D006801:Humans; D011493:Protein Kinase C / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000008:administration & dosage / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism; D011503:Transglutaminases / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured
D011503:Transglutaminases; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D013936:Thymidine