Inhibition of galectin-3 mediated cellular interactions by pectic polysaccharides from dietary sources

Abstract

Pectic polysaccharides from dietary sources such as Decalepis hamiltonii--swallow root (SRPP), Hemidesmus indicus (HPP), Nigella sativa--black cumin (BCPP), Andrographis serpyllifolia-(APP), Zingiber officinale--ginger (GRPP) and, citrus pectin (CPP) were examined for galectin inhibitory activity. Inhibition of (a) galectin-3 of MDA-MB-231 cells induced hemagglutination of red blood cells; (b) galectin-3 mediated interaction between normal/metastatic human buccal cells (NBC)/(MBC) and; (c) invasion of MDA-MB-231 and MBC in the invasive chamber was assessed. Results indicated that SRPP inhibited hemagglutination at Minimum Inhibitory Concentration (MIC) of 1.86 microg ml(-1) equivalent of carbohydrate as apposed to those of BCPP (130 microg ml(-1)), APP (40 microg ml(-1)), HPP (40 microg ml(-1)) and CPP (25 microg ml(-1)). GRPP even at concentration >1-6 mg ml(-1) did not inhibit agglutination. Also SRPP showed approximately 15 and 2 fold potent anti hemagglutination activity relative to that of galectin-3 specific sugars-galactose (MIC-27.1 microg ml(-1)) and lactose (MIC-4.16 microg ml(-1)) respectively. Further, SRPP at 10 microg ml(-1) inhibited agglutination of NBC by galectin-3 of MDA-MB-231 cells. Modified swallow root pectic polysaccharide (MSRPP) of 50 kDa retained anti hemagglutination activity (MIC of 1.03 microg ml(-1)) and inhibited MDA-MB-231 and MBC invasion by 73 and 50% with an IC(50) of 136 and 200 microg ml(-1) respectively. Both SRPP and MSRPP induced apoptosis up to 80% at 100 microg ml(-1) concentration by activating approximately 2 and 8 folds of Caspase-3 activity. Sugar composition analysis and its correlation with the galectin inhibitory property indicated that pectic polysaccharides with higher arabinose and galactose content-arabinogalactan inhibited hemagglutination significantly.