Identification of caffeoylquinic acid derivatives from Brazilian propolis as constituents involved in induction of granulocytic differentiation of HL-60 cells.
We have previously reported that Brazilian propolis extracts inhibited growth of HL-60 human myeloid leukemia cells, which is partly attributed to the induction of apoptosis associated with granulocytic differentiation. In this study, we isolated three compounds which induce granulocytic differentiation evaluated by nitroblue tetrazolium (NBT)-reducing assays from the water extract of propolis and identified as 4,5-di-O-caffeoylquinic, 3,5-di-O-caffeoylquinic, and 3,4-di-O-caffeoylquinic acids by NMR analysis. Cell growth inhibitory activity of these caffeoylquinic acids was found in HL-60 cell, which was mainly attributed to the induction of apoptosis. Furthermore, the potency of caffeoylquinic acid derivatives to induce granulocytic differentiation was examined in HL-60 cells. Caffeic, quinic, and chlorogenic acids had no effects on the NBT-reducing activity, while 3,4,5-tri-O-caffeoylquinic acid induced more than 30% of NBT-positive cells. These results suggest that the number of the caffeoyl groups bound to quinic acid plays an important role in the potency of the caffeoylquinic acid derivatives to induce granulocytic differentiation. This is the first report demonstrating that the caffeoylquinic acid derivatives induce granulocytic differentiation of HL-60 cells.
Mishima
Satoshi
S
Nagaragawa Research Center, API Co., Ltd., 692-3 Nagara, Gifu 502-0071, Japan.
Inoh
Yoshikazu
Y
Narita
Yukio
Y
Ohta
Shozo
S
Sakamoto
Takashi
T
Araki
Yoko
Y
Suzuki
Kazu-Michi
KM
Akao
Yukihiro
Y
Nozawa
Yoshinori
Y
D002454:Cell Differentiation / Q000187:drug effects*; D006098:Granulocytes / Q000187:drug effects*; D018922:HL-60 Cells; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D011429:Propolis / Q000737:chemistry*; D011801:Quinic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology
C472707:caffeoylquinic acid; D011801:Quinic Acid; D011429:Propolis