Caffeic acid phenyl ester in propolis is a strong inhibitor of matrix metalloproteinase-9 and invasion inhibitor: isolation and identification.
BACKGROUND
Propolis has been used as a folk medicine and has several proven biological activities. Herbal remedies recommended for cancer therapies in Korea.


METHODS
Matrix metalloproteinase (MMP)-9-inhibitory activity of propolis has been assessed. CAPE as an acting compound was isolated and molecular structure was determined. Anti-invasion activity of CAPE was assayed using hepatocarcinoma cells.


RESULTS
Propolis ethanol extracts showed a strong inhibitory effect of MMP-9 activity, which is known to be involved in tumor cell invasion and metastasis in a concentration-dependent manner on zymography. Assay guided fractionation led to the isolation of a caffeic acid phenyl ester (CAPE) as the compound responsible for the anti-MMP-9 activity. CAPE was obtained by reversed-phase HPLC, and its structure was elucidated by fast atom bombardment mass spectrometry and tandem mass spectrometry. The purified CAPE inhibited MMP-9 activity with the IC(50) of 1.0-2.0 nmol/l.


CONCLUSIONS
CAPE possesses selective antiproliferative activity toward hepatocaricoma cell line Hep3B, but not primary cultured mouse hepatocytes.
Jin
Un-Ho
UH
Department of Biochemistry and Molecular Biology, Dongguk University College of Oriental Medicine and National Research Laboratory for Glycobiology, Kyungbuk, Korea.
Chung
Tae-Wook
TW
Kang
Sung-Koo
SK
Suh
Seok-Jong
SJ
Kim
June-Ki
JK
Chung
Kang-Hyun
KH
Gu
Yeun-Hwa
YH
Suzuki
Ikukatsu
I
Kim
Cheorl-Ho
CH
D000818:Animals; D002109:Caffeic Acids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology / Q000473:pathology; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D015394:Molecular Structure; D009361:Neoplasm Invasiveness / Q000473:pathology; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives; D011429:Propolis / Q000737:chemistry*
D002109:Caffeic Acids; D061965:Matrix Metalloproteinase Inhibitors; D011429:Propolis; D020780:Matrix Metalloproteinase 9; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol