Lectin binding and effects in culture on human cancer and non-cancer cell lines: examination of issues of interest in drug design strategies.
By using a non-cancer and a cancer cell line originally from the same tissue (colon), coupled with testing lectins for cell binding and for their effects on these cell lines in culture, this study describes a simple multi-parameter approach that has revealed some interesting results that could be useful in drug development strategies. Two human cell lines, CCL-220/Colo320DM (human colon cancer cells, tumorigenic in nude mice) and CRL-1459/CCD-18Co (non-malignant human colon cells) were tested for their ability to bind to agarose microbeads derivatized with two lectins, peanut agglutinin (Arachis hypogaea agglutinin, PNA) and Dolichos biflorus agglutinin (DBA), and the effects of these lectins were assessed in culture using the MTT assay. Both cell lines bound to DBA-derivatized microbeads, and binding was inhibited by N-acetyl-D-galactosamine, but not by L-fucose. Neither cell line bound to PNA-derivatized microbeads. Despite the lack of lectin binding using the rapid microbead method, PNA was mitogenic in culture at some time points and its mitogenic effect displayed a reverse-dose response. This was also seen with effects of DBA on cells in culture. While this is a simple study, the results were statistically highly significant and suggest that: (1) agents may not need to bind strongly to cells to exert biological effects, (2) cell line pairs derived from diseased and non-diseased tissue can provide useful comparative data on potential drug effects and (3) very low concentrations of potential drugs might be initially tested experimentally because reverse-dose responses should be considered.
Petrossian
Karineh
K
Department of Biology and Center for Cancer and Developmental Biology, California State University Northridge, 18111 Nordhoff St. Northridge, CA 91330-8303, USA.
Banner
Lisa R
LR
Oppenheimer
Steven B
SB
D001681:Biological Assay / Q000379:methods; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D015195:Drug Design; D006801:Humans; D037102:Lectins / Q000378:metabolism* / Q000493:pharmacokinetics; D037121:Plant Lectins / Q000378:metabolism / Q000493:pharmacokinetics; D011485:Protein Binding
D037102:Lectins; D037121:Plant Lectins; C036554:dolichos biflorus agglutinin
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