Cytotoxic lectins (KML-C) were isolated from an extract of Korean mistletoe
[Viscum album C, (coloratum)] by affinity chromatography on a hydrolysed S
epharose 4B column, and the chemical and biological properties of KML-C wer
e examined, partly by comparing them with a lectin (EML-1) from European mi
stletoe[Viscum album L. (loranthaceae)]. The hemagglutinating activity of K
ML-C was inhibited by N-acetyl-D-galactosamine and D-galactose at the minim
um concentrations of 6.3 and 12.5 mu M/ml, respectively. Further biochemica
l analyses indicated that KML-C consists of four chains (M-r = 27.5, 30, 31
and 32.5 kDa) which, in some of the molecules, are disulfide-linked, and t
hat the chains of KML-C are distributed over a broad range of isoelectric p
oints (pI), 8.0 to 9.0, whereas the range for EML-1 is 6.6-7.0, A differenc
e was also observed between the N-terminal sequences of KML-C and EML-1. Th
e isolated lectins showed strong cytotoxicity against various human and mur
ine tumor cells, and the cytotoxic activity of KML-C was higher than that o
f EML-1. Tumor cells treated with KML-C exhibited typical patterns of apopt
otic cell death, such as apparent morphological changes and DNA fragmentati
on, and its apoptosis-inducing activity was blocked by addition of Zn2+, an
inhibitor of Ca2+/Mg2+-dependent endonucleases, in a dose-dependent manner
. These results suggest that KML-C is a novel lectin related to the cytotox
icity of Korean mistletoe, and that its cytotoxic activity against tumor ce
lls is due to apoptosis mediated by Ca2+/Mg2+-dependent endonucleases. (C)
1999 Published by Elsevier Science Ltd. All rights reserved.