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 Sepharose 4B column, and the chemical and biological properties of KML-C were examined, partly by comparing them with a lectin (EML-1) from European mistletoe[Viscum album L. (loranthaceae)]. The hemagglutinating activity of KML-C was inhibited by N-acetyl-D-galactosamine and D-galactose at the minimum concentrations of 6.3 and 12.5 microM/ml, respectively. Further biochemical analyses indicated that KML-C consists of four chains (Mr = 27.5, 30, 31 and 32.5 kDa) which, in some of the molecules, are disulfide-linked, and that the chains of KML-C are distributed over a broad range of isoelectric points (pI), 8.0 to 9.0, whereas the range for EML-1 is 6.6-7.0. A difference was also observed between the N-terminal sequences of KML-C and EML-1. The isolated lectins showed strong cytotoxicity against various human and murine tumor cells, and the cytotoxic activity of KML-C was higher than that of EML-1. Tumor cells treated with KML-C exhibited typical patterns of apoptotic cell death, such as apparent morphological changes and DNA fragmentation, 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 cytotoxicity of Korean mistletoe, and that its cytotoxic activity against tumor cells is due to apoptosis mediated by Ca2+/Mg2+ -dependent endonucleases.
Yoon
T J
TJ
Institute for Biomedical Research, Han Dong University, Pohang, Kyungbook, South Korea.
Yoo
Y C
YC
Kang
T B
TB
Shimazaki
K
K
Song
S K
SK
Lee
K H
KH
Kim
S H
SH
Park
C H
CH
Azuma
I
I
Kim
J B
JB
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005060:Europe; D006801:Humans; D007723:Korea; D037102:Lectins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D051379:Mice; D014784:Mistletoe; D009369:Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D037121:Plant Lectins; D010946:Plants, Medicinal; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D037102:Lectins; D010936:Plant Extracts; D037121:Plant Lectins