A phenolic compound, 5-caffeoylquinic acid (chlorogenic acid), is a new type and strong matrix metalloproteinase-9 inhibitor: isolation and identification from methanol extract of Euonymus alatus.
A phenolic compound responsible for anti-MMP-9, which is known to be involved in tumor cell invasion and metastasis, has been isolated from methanol extracts prepared from stem barks of Euonymus alatus by assay-guided fractionation. The compound has been identified as 5-caffeoylquinic acid (chlorogenic acid; CHA) by NMR and FAB-MS. CHA showed a strong inhibitory effect of matrix metalloproteinase (MMP)-9 activity in a concentration-dependent manner on zymography. The purified CHA inhibited MMP-9 activity with the IC50 of 30-50 nM. Furthermore, the cytotoxic survival curve showed that CHA does not have cytotoxic effects on cellular proliferation, when Hep3B cells were treated with various concentrations of CHA and cell viability was measured using the XTT assay. The present data suggest a clue for possible mechanisms of cancer chemoprevention by CHA and other naturally occurring phenolic compounds. The results also imply that useful cancer chemopreventive agents can be further identified by combinations of in vitro (as a first screen) and in vivo studies.
Jin
Un-Ho
UH
Department of Biochemistry and Molecular Biology, Dongguk University College of Oriental Medicine and National Research Laboratory for Glycobiology, Kyungju, Kyungbuk 780-714, Republic of Korea.
Lee
Ji-Young
JY
Kang
Sung-Koo
SK
Kim
June-Ki
JK
Park
Won-Hwan
WH
Kim
Jong-Guk
JG
Moon
Sung-Kwon
SK
Kim
Cheorl-Ho
CH
D045744:Cell Line, Tumor; D005591:Chemical Fractionation; D018890:Chemoprevention; D002726:Chlorogenic Acid / Q000737:chemistry* / Q000302:isolation & purification* / Q000627:therapeutic use; D029756:Euonymus / Q000737:chemistry*; D006801:Humans; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D061965:Matrix Metalloproteinase Inhibitors; D009369:Neoplasms / Q000188:drug therapy / Q000517:prevention & control*; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013778:Tetrazolium Salts
D061965:Matrix Metalloproteinase Inhibitors; D010936:Plant Extracts; D013778:Tetrazolium Salts; C059087:2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-((phenylamino)carbonyl)-2H-tetrazolium hydroxide; D002726:Chlorogenic Acid