Impact of alkyl esters of caffeic and ferulic acids on tumor cell proliferation, cyclooxygenase enzyme, and lipid peroxidation.
The antioxidant ferulic and caffeic acid phenolics are ubiquitous in plants and abundant in fruits and vegetables. We have synthesized a series of ferulic and caffeic acid esters and tested for tumor cell proliferation, cyclooxygenase enzymes (COX-1 and -2) and lipid peroxidation inhibitory activities in vitro. In the tumor cell proliferation assay, some of these esters showed excellent growth inhibition of colon cancer cells. Among the phenolics esters assayed, compounds 10 (C12-caffeate), 11 (C16-caffeate), 21 (C8-ferulate), and 23 (C12-ferulate) showed strong growth inhibition with IC50 values of 16.55, 13.46, 18.67, and 7.57 microg/mL in a breast cancer cell line; 9.65, 7.45, 17.05, and 4.35 microg/ mL in a lung cancer cell line; 5.78, 3.5, 4.29, and 2.46 microg/mL in a colon cancer cell line; 12.04, 12.21, 14.63, and 8.09 microg/ mL in a central nervous system cancer cell line; and 8.62, 7.76, 11.0, and 5.37 in a gastric cancer cell line. In COX enzyme inhibitory assays, ferulic and caffeic acid esters significantly inhibited both COX-1 and COX-2 enzymes. Caffeates 5-10 (C4-C12), inhibited COX-1 enzyme between 50% and 90% and COX-2 enzyme by about 70%, whereas ferulates 15-21 (C3-C8) inhibited COX-1 and COX-2 enzymes by 85-95% 25 microg/mL. Long-chain caffeates 11-14 (C16-C22) and short-chain ferulates 15-20 (C3-C5) were the most active in lipid peroxidation inhibition and showed 60-70% activity at 5 microg/mL concentration.
Jayaprakasam
Bolleddula
B
Bioactive Natural Products and Phytoceuticals, Department of Horticulture and National Food Safety and Toxicology Center, Michigan State University, East Lansing, Michigan 48824, USA.
Vanisree
Mulabagal
M
Zhang
Yanjun
Y
Dewitt
David L
DL
Nair
Muraleedharan G
MG
D002109:Caffeic Acids / Q000138:chemical synthesis / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects*; D045744:Cell Line, Tumor; D003373:Coumaric Acids / Q000737:chemistry / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004952:Esters / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects*; D009682:Magnetic Resonance Spectroscopy; D009369:Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*
D002109:Caffeic Acids; D003373:Coumaric Acids; D016861:Cyclooxygenase Inhibitors; D004952:Esters; C004999:ferulic acid; D011451:Prostaglandin-Endoperoxide Synthases