Lectins isolated from Korean mistletoe (Viscum album coloratum) induce apoptosis in tumor cells

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.