Cinnamic acid inhibits proliferation and modulates brush border membrane enzyme activities in Caco-2 cells.
The objective of the present study was to examine whether cinnamic acid exerts antitumor activity against colon cancer cells in vitro. For this purpose we investigated the effect of cinnamic acid on cell proliferation and on the differentiation markers alkaline phosphatase, sucrase and aminopeptidase N in human colon adenocarcinoma cells (Caco-2). Cinnamic acid (2.5-8.0 mM) prolonged the doubling time and inhibited the DNA synthesis of growing cells. The antiproliferative effect occurred rapidly after 2 h of treatment with 8.0 mM cinnamic acid and reached nearly maximal values after 8 h of treatment. Sucrase and aminopeptidase N activities were stimulated under cinnamic acid treatment (4.0-8.0 mM), while alkaline phosphatase activity was inhibited in postconfluent cells (8.0 mM). Similar effects on enzyme activities were seen in non-proliferating cells. Cinnamic acid did not alter the adhesion to collagen matrix or cell viability. Intracellular cAMP levels were decreased significantly after 1 h of treatment with 8.0 mM cinnamic acid, suggesting that cinnamic acid induces its effects on enzyme activities partly by modulating the cAMP signaling pathway.
Department of Medical Physiology, University of Vienna Medical School, Austria. cem.ekmekcioglu@univie.ac.at
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D000262:Adenylyl Cyclases / Q000187:drug effects / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D018938:Caco-2 Cells / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology*; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002934:Cinnamates / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008871:Microvilli / Q000201:enzymology; D013778:Tetrazolium Salts; D013844:Thiazoles
D000970:Antineoplastic Agents; D002934:Cinnamates; D004273:DNA, Neoplasm; D013778:Tetrazolium Salts; D013844:Thiazoles; C029010:cinnamic acid; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; C022616:thiazolyl blue