Wheatgerm agglutinin mediated toxicity in pancreatic cancer cells

Citation
Re. Schwarz et al., Wheatgerm agglutinin mediated toxicity in pancreatic cancer cells, BR J CANC, 80(11), 1999, pp. 1754-1762
Citations number
74
Categorie Soggetti
Oncology,"Onconogenesis & Cancer Research
Journal title
BRITISH JOURNAL OF CANCER
ISSN journal
00070920 → ACNP
Volume
80
Issue
11
Year of publication
1999
Pages
1754 - 1762
Database
ISI
SICI code
0007-0920(199908)80:11<1754:WAMTIP>2.0.ZU;2-P
Abstract
Lectin binding specificities for carbohydrate allow phenotypic and function al characterization of membrane-associated glycoproteins expressed on cance r cells. This analysis examined wheatgerm agglutinin binding to pancreatic cancer cells in vitro and the resulting toxicity. Membrane preparations of nine human pancreatic carcinoma cell lines were studied for lectin binding using wheatgerm agglutinin (WGA), concanavalin A (ConA) and phytohaemagglut inin-L (PHA-L) in a lectin blot analysis. Cell proliferation in vitro was m easured by thymidine incorporation in the absence or presence of lectins at Various concentrations. Sialic acid binding lectins or succinyl-WGA (succW GA) served as controls. WGA toxicity was tested after swainsonine or neuram inidase pretreatment. Binding and uptake of fluorescein-labelled lectins wa s studied under fluorescence microscopy. All pancreatic cell lines displaye d high WGA membrane binding; primarily to sialic acid residues. Other lecti ns were bound with weak to moderate intensity only. Lectin toxicity corresp onded to membrane binding intensity and was profound in case of MGA (ID50 a t 2.5-5 mu g ml(-1)). WGA exposure induced chromatin condensation;nuclear f ragmentation and DNA release consistent with apoptosis. important steps for WGA toxicity included binding to sialic acid on swainsonine-sensitive carb ohydrate and lectin internalization, There was rapid cellular uptake and su bsequent nuclear relocalization of WGA. in contradistinction to the other l ectins studied, WGA proved highly toxic to human pancreatic carcinoma cells in vitro. WGA binding to sialic acid residues of N-linked carbohydrate, ce llular uptake and subsequent affinity to N-acetyl glucosamine appear to be necessary steps. Further analysis of this mechanism of profound toxicity ma y provide insight relevant to the treatment of pancreatic cancer.