Cancer chemopreventive and anti-inflammatory activities of chemically modified guar gum.
Guar gum (G) is a simple characterized branched polysaccharide, which is frequently used in food industries. We prepared the gum C-glycosylated derivative (GG), and its sulphated derivative (SGG), aiming to characterize their cancer chemopreventive, and anti-inflammatory properties. Estimation of cancer chemopreventive activity, specifically anti-initiation, including the modulation of carcinogen metabolism and the antioxidant capacity, revealed that GG was a potent anti-initiator, where it inhibited not only the carcinogen activator enzyme, cytochrome P450 1A (CYP1A), but also induced the carcinogen detoxification enzymes glutathione-S-transferases (GSTs), while SGG inhibited both CYP1A and GSTs. SGG was an effective radical scavenger than GG against hydroxyl, peroxyl, and superoxide anion radicals. GG and SGG were found to modulate the macrophage functions into an anti-inflammatory pattern. Thus, both enhanced the macrophage proliferation and phagocytosis of fluorescein isothiocyanate (FITC)-zymosan; however, they also inhibited strongly the nitric oxide generation and tumor necrosis factor-alpha secretion in lipopolysaccharide (LPS)-stimulated RAW macrophage 264.7. Unexpectedly, both GG and SGG dramatically inhibited the binding affinity of FITC-LPS to RAW 264.7, as indicated by flow cytometry analysis. GG and SGG exhibited a significant anti-proliferative activity against human hepatocellular carcinoma cells (Hep G2), and only SGG was specifically cytotoxic for human breast carcinoma cells (MCF-7), but neither was significantly cytotoxic for human lymphoblastic leukemia cells (1301). SGG led to a major disturbance in cell cycle phases of Hep G2 cells as indicated by concomitant arrest in S- and G2/M-phases, a disturbance that was associated with an induced cell death as a result of necrosis, but not apoptosis in both GG- and SGG-treated cells. Taken together, the modified gums could be used as an alternative of G in health food industries to provide cancer prevention in risk populations.
Gamal-Eldeen
Amira M
AM
Cancer Biology Laboratory, Department of Biochemistry, Division of Genetic Engineering and Biotechnology, National Research Centre, Dokki 12622, Cairo, Egypt. aeldeen@hotmail.com
Amer
Hassan
H
Helmy
Wafaa A
WA
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry* / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D005685:Galactans / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D008264:Macrophages / Q000187:drug effects; D008351:Mannans / Q000737:chemistry* / Q000494:pharmacology*; D051379:Mice; D009369:Neoplasms / Q000473:pathology* / Q000517:prevention & control*; D053149:Plant Gums
D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D000975:Antioxidants; D005685:Galactans; D008351:Mannans; D053149:Plant Gums; C007894:guar gum